Cancer - an overview | ScienceDirect Topics
Chapters and Articles
You might find these chapters and articles relevant to this topic.
According to National Cancer Institute (NCI), cancer is a term used to describe diseases characterized by abnormal and uncontrolled division of cells and, which can invade nearby tissues and may or may not spread to other body parts via systemic circulation and lymphatic system [68]. Since its realization, huge advances have been made in the field with increased understanding of the pathophysiology and causes of the disease though barriers still exist in its treatment [69]. One such barrier was production of the personalized replica model to practice and preplan surgery of the cancer patient to precisely target tumor and achieve high efficiency in chemotherapy [70]. Advances in 3D printing technology have enabled fabrication of in vitro models to mimic and understand tumor development and metastasis [71]. It is particularly useful in engineering of the cell microenvironment as it allows precise spatial control of the cell organization and insertion of biomolecules [72]. Along with the basic structure, it is also capable of incorporating various cell types, polymers, vasculature and micro-channels to mimic the tissues or organs [73]. This provides a clinical platform to predict the pattern of tumor cell proliferation and accurately locate the malignancy thereby increasing precision of treatment approaches and a further scope in advancement relating to better understanding of the disease and hence its treatment [74].12.1 Cancer
URL:
https://www.sciencedirect.com/science/article/pii/S0753332218318407
Cancer is a well-known, incapacitating, and potentially deadly disease affecting many individuals and their families across all sociodemographic spectra (e.g., age, sex, race, and ethnicity, education level, occupation and income, social class, spirituality, faith and religion, and culture) in diverse communities throughout the world. Cancer is the second leading cause of death worldwide at all income levels. In 2012, the worldwide incidence of cancer – excluding nonmelanoma skin cancers – was estimated at 14.1 million. The corresponding estimate for worldwide cancer-related deaths was 8.2 million in 2012 (American Cancer Society, 2015). Global and national estimates of cancer incidence and mortality are well documented (American Cancer Society, 2014, 2015; Stewart and Wild, 2014; Ferlay et al., 2015; National Cancer Institute, 2016). However, the incidence and severity of cancer and treatment-related biobehavioral adverse effects are generally not well known. For example, cancer and treatment-related cognitive impairments (e.g., problems in cognitive processes and behavioral outcomes such as attention and memory), the clinical course of this adverse condition, reliable methods for assessing its presence and severity, and possible effective interventions to help mitigate its impact on cancer patients' and survivors' psychosocial functioning and overall quality of life are not well characterized. Malignant tumors and their treatments are associated with adverse effects that can negatively impact patients and survivors on multiple biobehavioral (e.g., fatigue, pain, peripheral neuropathy, nausea and emesis, and sleep impairments), neurocognitive (e.g., impairments in attention and memory, information-processing speed, and executive functioning), psychologic (e.g., anxiety, depression, self-perception, coping strategies, and life adjustment), and sociorelational (e.g., familial and interpersonal relationships) dimensions (van Dam et al., 1998; Wefel et al., 2004; Falleti et al., 2005; Vardy and Tannock, 2007; Dietrich et al., 2008; Luckett et al., 2011; Ganz, 2012; Myers, 2012; Cleeland et al., 2013; Sales et al., 2014; Faller et al., 2015; Kenzik et al., 2015; Kurita and Sjogren, 2015; Mackenzie, 2015; Saita et al., 2015). Relative to the data available regarding cancer mortality, however, cancer and treatment-related biobehavioral, neurocognitive, psychologic, and sociorelational sequelae are not well understood. Consequently, systematic efforts and strategies to alleviate the burden and suffering of these adverse conditions are still lacking. Difficulties understanding and treating adverse effects of cancer and its treatments are particularly salient when dealing with neurocognitive sequelae of noncentral nervous system (CNS) cancers, where the underlying etiology is yet to be fully characterized. Brain cancers (e.g., astrocytoma, glioblastoma, glioma, medulloblastoma, and meningioma) and to some degree spinal cord cancers (including intramedullary and extramedullary tumors) and related treatment (e.g., neurosurgery, CNS-targeted radiotherapy, intrathecal chemotherapy) commonly cause neurocognitive dysfunction as a result of direct insult to CNS tissues, and patients are routinely counseled regarding the likelihood of these effects (Behin and Delattre, 2004; Schiff et al., 2015). In contrast, the detrimental cognitive sequelae resulting from non-CNS cancers (e.g., breast, colorectal, cervical, and prostate carcinomas) and their treatment would not be as readily expected given the lack of direct insult to the CNS. While awareness of these potential effects has increased dramatically in recent years, there remain important limitations in our understanding of the mechanisms underlying these changes, and few available resources with regard to prevention and treatment. In the present chapter, we examine the effects of adult-onset non-CNS malignancies and their various treatments on neurocognitive functioning from a neuroepidemiologic perspective. Specifically, we present a brief overview of the concept of cancer and treatment-related neurocognitive dysfunction (CRND), its clinical presentation (e.g., presenting symptoms and complaints), descriptive epidemiology (e.g., incidence, prevalence, and mortality), pathophysiology (e.g., functional changes that normally accompany CRND), factors that enable its development and maintenance, and ongoing efforts (e.g., clinical trials of behavioral and pharmacologic interventions) to mitigate this detrimental neurocognitive ailment for cancer patients and survivors throughout the cancer diagnosis, care, and survivorship continuum.Introduction
URL:
https://www.sciencedirect.com/science/article/pii/B9780128029732000173
Cancer is a disease that develops overtime, through the accumulation of mutations and genetic changes in a cell [1]. Several characteristics distinguish cancerous cells from the normal ones, including a sustained proliferative ability, induction of angiogenesis, evasion of growth suppressors, resistance to cell death, replicative immortality, the ability to invade and metastasize, evading immune attack, genomic instability, inflammation, and continuous production of energy, all these being collectively designated as the “hallmarks of cancer” [2]. Cancer is one of the most devastating and haunting diseases, affecting the lives of millions around the globe [3]. Despite the immense efforts involved in cancer research, prevention, detection, and treatment, the number of cancer cases has continued to increase [1, 4]. According to the World Health Organization and the International Agency for Cancer Research, there were 18.1 million new cancer cases and 9.6 million cancer deaths in 2018 [5]. In both sexes combined, lung cancer was the most commonly diagnosed cancer (11.6% of the total cases), as well as the leading cause of cancer death, closely followed by female breast cancer, prostate cancer, and colorectal cancer in terms of incidence. Moreover, malignant neoplasms are ranked the second leading cause of deaths worldwide after cardiovascular diseases [6]. Unfortunately, these worrying estimates are expected to heavily increase in the following years, which constitutes a ringing alarm [5]. Conventional strategies for cancer treatment involve surgery, radiotherapy, immunotherapy, and chemotherapy, depending upon the cancer type, as well as its clinical stage, chemotherapy being the upfront method of disease management in clinically advanced solid malignancies and hematopoietic cancers [1]. Chemotherapy represents one of the main alternatives for cancer treatment, employing a wide group of drugs, including specific molecules capable of inhibiting proliferative signaling pathways, replicative immortality mechanisms, and angiogenesis, as well as inducing the apoptosis of tumor cells [7]. Based on their origins or mechanisms of action, chemotherapeutic agents are broadly classified into different groups such as alkylating agents, cell-cycle inhibitors, antimetabolites, microtubule-damaging agents, antibiotics, targeted antibodies or topoisomerase and small molecule inhibitors, the ultimate goal of chemotherapy being the elimination of tumor cells [1].Introduction
URL:
https://www.sciencedirect.com/science/article/pii/B9780128207017000099
Cancer is a unique area in which to study the effects of new agents, particularly in the treatment of advanced disease. The ultimate goal is to increase survival. The earlier detection of disease and the increase of new agents available to treat the disease have resulted in a concerted effort to continue to improve treatment. This has been met with some success. More patients with cancer are surviving for longer, though, there has been little change in the survival statistics for those with advanced lung cancer, the commonest fatal malignancy in the world. The incidence of lung cancer in men in Scotland is falling, due mainly to fewer men smoking, however the incidence in Scottish women continues to rise, because more women smoke. Lung cancer now accounts for more cancer deaths than breast cancer [5, 6]. Recent work in breast cancer suggests that for the first time, survival is improving; the most likely explanation is the increased use of mammography in the last 15 years and improved systemic adjuvant chemotherapy [7].
URL:
https://www.sciencedirect.com/science/article/pii/S1040842898000250
Cancer is considered a highly heterogeneous and complex genetic disease that drives the progressive transformation of normal cells into malignancy by a multistep and sequential ordered process. However, and in addition to the contribution of genetic mutations in the well established cancer genes (oncogenes and tumor suppressors), the onset and progression of cancer is also bound to the cancer cell's microenvironment and to other epigenetic events that contribute to funnel the cell into malignancy. In this regard, large projects aimed at deciphering the genetic changes occurring in tumors are being questioned due to their limited applicability for the development of effective therapies [1]. These arguments [1,2] suggest that the development of an effective therapy against cancer will require the targeting of the biological pathways commonly altered in the cancer cell [1–5]. A starting point for this change of gear was the admirable summary of the phenotype of the cancer cell in the following six traits: an unlimited replicative potential, sustained angiogenesis, evasion of apoptosis, self-sufficiency in growth signals, insensitivity to anti-growth signals and tissue invasion and metastasis [2]. Quite recently, the so-called “metabolic reprogramming” of the cancer cell has been added as a seventh hallmark of the cancer phenotype [3,5].
URL:
https://www.sciencedirect.com/science/article/pii/S0925443909000210
Cancer is a disease of the genome, arising out of a sophisticated interplay between thousands of genes, forming intricate pathways to carry out all levels of cellular function and subject to the lifelong influence of varied and unpredictable environmental factors. There are myriad routes of oncogenesis, reflecting complex interactions between forces acting at the level of the DNA sequence and its epigenetic framework, the gene expression machinery and subsequent RNA processing, and the protein itself. There is the power to interrogate all of these processes on a genome-wide scale using high-throughput technologies, such as next-generation sequencing (NGS). The number of raw data points generated through these experiments, coupled with the necessity of integrating multiple levels of data to discern meaningful information, brings about a combinatorial explosion of analytical dimensions. The sheer size of these data sets is a humbling illustration of the magnitude of the task: to identify recurrent patterns amid the sea of available data and to exploit them for clinical gain. Malignancy of the foregut is common and carries a poor prognosis, with overall 5-year survival rates of 18.8% and 30.6% in the esophagus and stomach, respectively.1 Management paradigms vary dramatically between primary esophageal tumors and gastric tumors, and few targeted therapies exist for either. With increasing knowledge of the genomic underpinnings of upper gastrointestinal malignancies, driven largely by the utilization of high-throughput sequencing technologies, more sophisticated, molecularly based classification systems are being developed, in the hope of devising rational treatment approaches based more on a tumor’s specific genomic drivers than on its anatomic site.Introduction
URL:
https://www.sciencedirect.com/science/article/pii/S0039610919300052
Cancer is a complex human disease that is characterized by uncontrolled growth and spread of abnormal cells potentially affecting almost any tissue in the body. It is overtaking heart disease as the no. 1 killer in the USA. An estimated 569 490 Americans will die from cancer in 2010 alone, according to the American Cancer Society, and the worldwide incidence of cancer continues to increase [1]. In fact, cancer is not a single disease but a conglomerate of many diseases caused by the accumulation of multiple molecular alterations in the genetic material. In recent years, many cancer patients have benefited from improved treatments, including surgery, chemotherapy, targeted therapies, and radiation therapy. However, success is often marginal and serious side effects are common and the outcome remains disappointing, especially for those patients with advanced cancer. For instance, surgery followed by systemic chemotherapy and radiotherapy is only recommended for the subset of cancer patients who have been fortunate to have their disease completely resected. Although radiotherapy eradicates cancer cells and prevents disease recurrence to a certain degree, it can only be administered to a specific region and its delivery and dose are limited to organs within the radiation field. Chemotherapy kills actively dividing cells including cancer cells, but its administration is limited because of severe toxicity to non-cancer cells. Furthermore, many improvements in survival obtained in certain type of cancers have not been observed in most advanced cancers because they are often diagnosed late and thus systemic therapies are limited. Most patients die from the malignancy within a year of their diagnosis, despite extensive surgical resection and aggressive adjuvant radiotherapy and chemotheray. Thus, it is clear that development of techniques augmenting diagnosis of cancer at an early stage and/or better adjuvant therapies will significantly improve patients survival and help cancer management. Development of novel imaging techniques has currently improved our ability to detect cancers at earlier stages, quantify invasion or metastasis, or monitor therapeutic responses [2]. In previous decades, structural abnormalities relative to the diseases or treatment efficacy were usually determined by conventional imaging modalities which relied largely on monitoring the change of gross anatomy. Recently, with advances in imaging instrumentations and imaging agents, it has become possible to image or characterize the biological processes at the cellular, subcellular, or even the molecular level in living subjects [2–4]. As a result, a new discipline known as molecular imaging has emerged in the field of biomedical research [4]. Indeed, the approaches developed in molecular imaging provide essential breakthroughs in the fight against cancer. Combining molecular biology, imaging instruments as well as molecular probes, novel imaging techniques not only display high sensitivity for detecting cancer at a molecular level but also provide high spatial resolution. Many molecular imaging modalities, such as magnetic resonance imaging (MRI), nuclear imaging (i.e. single-photon-emission computed tomograpy [SPECT], single-photon-emission tomography [PET]), x-ray computed tomography (CT), optical imaging and ultrasound imaging, have become indispensable for the clinic [2–7]. Depending on the clinical need, relevant molecular imaging modalities are chosen for detecting both primary and metastatic tumors and monitoring cancer-associated physiological processes in real-time. Importantly, these techniques are all non-invasive and can provide complementary information for cancer diagnosis. For example, due to its excellent soft-tissue contrast properties and high spatial resolution (pixel dimension of 10–100 μm), MRI enables sensitive detection of soft-tissue pathologies, and provides quantitative morphometric information and valuable physiological readouts [2]. As a classical anatomical imaging modality, CT can non-invasively produce images as rich in anatomical information as MRI. Consequently, CT is primarily used to display internal anatomy of living subjects, especially skeletal structures and the lung. However, the sensitivity of both MRI and CT is insufficient to detect abnormalities at the cellular or molecular level. In contrast, nuclear imaging techniques (PET or SPECT), dependent on the availability of radioactive molecular probes, can provide the high detection sensitivity required for monitoring the biomarkers associated with cancers. Optical imaging techniques, such as fluorescence and bioluminescence imaging, provide fast and highly sensitive approaches to map specific molecular targets in vivo. However, either nuclear or optical imaging has limited capability in producing anatomical information. Therefore, it is necessary to develop multimodal imaging strategies to validate fully the results of each single molecular imaging technique. Recent advances in cancer molecular imaging were successfully made through combining different imaging modalities (PET-CT, PET-MRI, MRI-optical, etc.) in order to enhance synergistically overall sensitivity and specificity. Table 15.1 provides an overview of imaging systems. TABLE 1. Overview of Imaging Systems Cost of system: $: <100 000; $$: 100–300 000; $$$: >300 000. Nanotechnology, as a multidisciplinary reseach field that involves chemistry, engineering, biology, physics and material science, leads to a generation of new diagnostic and therapeutic agents for early cancer detection and personalized treatment. This hopefully will result in dramatically improved outcomes [3,4,8]. In the field of cancer diagnosis, molecular imaging takes advantage of both conventional and newly emerging imaging techniques and sometimes requires the administration of molecular probes to measure cancer biomarkers. However, it is still challenging to design and develop desirable molecular probes that have the ability specifically to reach the target of interest and display high target to non-target signal ratio in vivo. Thus far, most molecular probes available to the clinic are small molecule-based radioactive probes. Recent advances in nanotechnology have resulted in an unprecedented development of nanoparticle-based molecular probes [4,8]. Engineered nanomaterials have the potential to revolutionize early cancer detection and personalized cancer management by augmenting the sensivity and specificity of the “state of the art” imaging techniques. The engineered nanomaterials exhibit superior physical and chemical properties when their sizes are smaller than several tenths to hundredths of nanometers, arguably due to large relative surface area and dominant quantum confinement effects. Nanomaterials typically have a size range of 1–100 nm, comparable to most biological functional units, such as enzymes, antibodies and receptors. Furthermore, the decrease in the particle size dramatically increases the reactivity of nanomaterials and enhances their ability to couple with various functional moities. As a result, engineered nanomaterials are capable of maintaining the stability and specificity within the biological environment in order to allow unique interaction with biological systems at the molecular level. Moreover, nanomaterials usually have uniform size and shape so that each individual nanoparticle (NP) has nearly identical physical and chemical properties for controlled biodistribution, bioelimination and contrast effects. When nanoparticles are administered in the bloodstream, their size and surface properties favor extravasation through leaky vasculature, followed by deep penetration and retention at the tumor sites, which is a phenomenon known as the enhanced permeability and retention (EPR) effect. Once immobilized with targeting moieties, the nanoparticles can actively accumulate in tumors by the specific binding with tumor-associated biomarkers such as over-expressed receptors, tumor extracellular matrix and enzymes (Figure 15.1). FIGURE 15.1. (A) Multifunctional nanoparticles (NP). Coupled with biological targeting agents and drug molecules, such multifunctional NPs have shown great promise as target-specific delivery vehicles with enhanced imaging sensitivity and therapeutic efficacy. (B) Behavior of nanoparticles in blood vessels in the liver, normal tissue, and tumor tissue regions. The enhanced permeability and retention (EPR) effect of the tailored multifunctional NPs is greatest at cancer cells. See color plate section. Typically, nanomaterials suitable for moleuclar imaging include organic nanoparticles (such as liposomes, polymer vesicles) or inorganic nanoparticles (such as metal NPs, carbon nanotubes, metal oxide NPs, quantum dots). Among various nanoparticles, inorganic nanomaterials have been extensively used as molecular probes because of their superior optical, electrical and magnetic properties, leading to significant enhancement in imaging contrast. For example, superparamagnetic iron oxide nanoparticles have been used as contrast agents for MRI. Gold-based nanoparticles, such as gold rods, gold nanoshells and gold nanocages, have been extensively investigated due to their unique surface plasmon resonance (SPR) in optical imaging, Raman spectroscopy and photoacoustic imaging. Quantum dots have recently received immense attention in cancer imaging because of their attractive fluorescent properties. Compared to conventional molecular platforms used for imaging, the use of nanoparticle-based molecular probes shows several distinctive advantages and has great potential in both non-invasive detection as well as the treatment monitoring of human cancers. First, multifunctionality is a key advantage of nanomaterial-based imaging probes for cancer diagnosis. Through systematic conjugation with different targeting moieties, contrast enhancers, permeation enhancers, or even therapeutic agents, various molecular imaging nanoprobes can bypass biological barriers, achieve the capability to recognize tumor-specific biomarkers, and visualize and quantify tumor growth or regression during therapy with improved imaging sensitivity and specificity. Oftentimes, multiple modalities are involved. Secondly, many nanomaterials possess unique physical properties which can be used as sensors/reporters for molecular imaging applications, and these properties simply cannot be achieved by other molecular platforms. Furthermore, the unique and diverse physical and chemical properties of nanoprobes are derived from the composition, size and shape of relevant nanomaterials. Because each individual nanoprobe has nearly identical physical and chemical properties, they can be designed to have the ability to detect a large number of different biomarkers at the same time to provide sufficient information needed to characterize cancers, which is known as multiplexing. Thirdly, engineered nanomaterials can potentially alter and improve the pharmacokinetics of molecular probes in vivo. By coating nanomaterials with biocompatible polymers, the circulation half-life of molecular probes can be extended to have more opportunities to penetrate though vascular endothelium and reach the desired sites while minimizing uptake by the reticuloendothelial system (RES). All these advantages indicate that nanoprobes can play important roles in cancer diagnosis. With the ongoing efforts to enhance their targeting ability and endow more functions, the future of nanomaterial-based molecular imaging probes is highly promising. This chapter summarizes some of the most recent developments of nanomaterials in state-of-the-art molecular imaging and highlights their impact on cancer diagnosis.Introduction
Technique Resolution Depth Time Representative Imaging Agents Cost Magnetic resonance imaging (MRI) 10–100 μm No limit Min–hours Gadolinium-doped NPs, iron oxide NP $$$ X-ray computed tomography (CT) 50 μm No limit Min Iodine- or gadolinium- doped NPs, Au NPs, Bi2S3 NPs, TaOx NPs $$ Ultrasound imaging 50 μm mm Min Microbubbles, perfluorocarbon (PFC) emulsion NPs $$ Positron emission tomography (PET) imaging 1–2 mm No limit Min 64Cu-labeled NPs, 64CuS NPs $$$ Single photon emission tomography (SPECT) imaging 1–2 mm No limit Min 111In-labeled NPs $$ Fluorescence imaging 1–2 mm <1 cm Min NIR fluorochromes, quantum dot $ Bioluminescence imaging (BLI) 1–2 mm cm Min Luciferin $ Raman imaging 1–2 mm cm Min Gold rods, gold nanocages, gold nanoshells, carbon nanotubes $$ Photoacoustic imaging (PAI) 250 μm cm Min–hours Gold rods, gold nanocages, gold nanoshells, carbon nanotubes $$ 
URL:
https://www.sciencedirect.com/science/article/pii/B9780123869401000155
The term cancer is used to designate a set of diseases whose principal characteristic is the disordered and abnormal growth of cells, which undergo changes in their genetic material and divide rapidly, invading tissues and organs (Borges et al., 2008). These cells become less specialized in their functions and can be aggressive and uncontrollable, causing the formation of tumors, which can spread to other regions of the body. The unique types of cancer correspond to the various cells in the body and can appear in any region of the body. However, some organs are more affected than others, and each organ can be affected by different tumors, more or less aggressive, and the altered cells can spread, reaching organs distant from the place where the tumor started, forming metastases (Almeida et al., 2005). Cancer is the main public health problem in the world and a major cause of death in most countries. In women, according to the most recent world estimate, of the year 2018, breast cancer (24,2%), colon and rectum (9,5%), lung (8,4%) and cérvix (6,6%) were the most frequent types of cancer (Bray et al., 2018). The rates of breast cancer predominate regardless of the country's socioeconomic status, its incidence being among the first positions of female malignancies. In countries with low and medium Human Development Index (HDI), the second most incident is cervical cancer. In the Northeast Region of Brazil, without considering non-melanoma skin tumors, cervical cancer is the second most incident (17.62/100 thousand) (INCA 2019). Cancer of the female pelvic location can affect gynecological structures of the reproductive system. This refers to a malignant condition of the female reproductive system that can include the body and cervix, ovaries, vulva, vagina and endometrium (Gupta and Rajwanshi 2013, Rutledge et al., 2010). The treatment of gynecological cancer depends on the stage of the disease, it is determined according to a classification system that establishes the extent of the cancer present in the body, its spread and its location (A.C. Camargo Cancer Center, 2018). Gynecological cancer therapy can include surgery, radiation therapy, chemotherapy, hormone therapy and target therapy or a combination of these modalities (Rutledge et al., 2010). Women with gynecological cancer, especially ovarian cancer, often receive complex and aggressive treatments. Usually, the primary treatment is surgery (Mccorkle et al., 2009), which is one of the most frequent and appropriate forms of treatment for most malignancies (Soares and Silva 2010). Despite the great advances in these therapies provide greater survival and great impact on the quality of life of women, there are still disorders that these therapies, alone or combined, can affect in the pelvic organs and lead to disorders of the pelvic floor (PF), in their anatomophysiology (Ramaseshan et al., 2018). A diagnosis of gynecological cancer affects several aspects of a woman's life, including the state of physical and psychological health (Maqbali et al., 2019). Thus, performing a multi-professional team at different levels of disease staging is essential, regardless of the therapeutic method adopted. Since they present essential skills that complement each other. Among them, oncological physiotherapy stands out. This is a recognized specialty, which aims to preserve and restore the kinetic-functional integrity of organs and systems, besides preventing disorders caused by cancer treatment (Faria 2010). Your contribution to the multi-professional team is essential, from the prevention of sequelae to their rehabilitation, to minimize or overcome adverse effects arising from unique types of treatment, besides palliative treatment. Resources contribute to both the improvement of symptoms and the quality of life (Maués et al., 2017). There are studies that show the positive results of physical therapy care and the evolution in the development of its techniques and resources, in the treatment of cancer, mainly in the return to functionality, as in mastectomized women, for example (Luz & Lima 2011). However, there is a shortage of articles that address the treatment of physiotherapy in gynecological cancer. Thus, it is necessary to investigate, know and evidence the contributions that physiotherapy can promote in other manifestations of the disease and explore the evolution of resources and/or techniques applied. Therefore, the aim was perform a systematic review of the effectiveness of physiotherapy as an adjunct treatment in patients with gynecological cancer.1 Introduction
URL:
https://www.sciencedirect.com/science/article/pii/S1360859221001467
Cancer is a disease that has always been a part of the human life. References to cancer have been found in numerous early sources, some of which are thousands of years old. The most ancient descriptions of tumors and cancer treatment methods are the ancient Egyptian papyruses dated roughly to 1600 BC (Bozzone, 2009). From this source, we know that the Egyptians used cauterizing ointments containing arsenic for the treatment of superficial tumors. Similar descriptions were found in the manuscripts of ancient India, which described surgical removal of tumors and the use of arsenic ointments (Bozzone, 2009). The term “cancer” itself was introduced by Hippocrates, who described and investigated various tumors, including those of breast, stomach, skin, cervix, rectum, and throat (Figure 1.1). Hippocrates noticed that all the cancers have a visual similarity to a crab (Greek, karkinos) because of characteristic outgrowths aimed in opposite directions. Regarding the treatment of cancer, Hippocrates proposed the surgical removal of available tumors followed by treatment of postoperative wounds with ointments containing either plant poisons or arsenic, which were supposed to kill the remaining cancer cells. In cases of internal tumors, Hippocrates suggested to give up any kind of treatment, because he believed that the consequences of such a complex operation will kill the patient faster than the tumor itself. Figure 1.1. Hippocrates of Cos (460–370 BC) was an ancient Greek physician and philosopher. Nowadays, we understand cancer as a pathological condition of the body where cells grow and reproduce in an uncontrollable manner. Alternatively, cancer is referred to as a large group of diseases characterized by disorganized and unregulated cell division. To date, more than 200 different cancers are known. Importantly, almost every cell of an organism may give rise to cancer; therefore, cancer is rather regarded as a disease of a cell than a disease of an organ. Cancer cells grow and form tumors, which are classified according to their clinical and morphological features in two main groups, namely, benign and malignant tumors. Benign tumors are characterized by a slow expansive growth, the absence of metastases, and no overall effect on the body; thus, they are regarded as noncancerous. Instead, malignant tumors are highly cancerous, which means they have several typical features, such as rapid progression, tendency to infiltration, high metastatic potential, and frequency of recurrence. In everyday practice, the term “cancer” is commonly used as a synonym for malignant tumor, and it should also be mentioned that in our book we will consider malignant tumors only. The overall effect of malignant tumors is often manifested by significant weight loss, various metabolic disturbances, skin changes, fatigue, fever, pain, and, ultimately, development of cachexia. Other general symptoms and signs may also include bleeding, indigestion, and emergence of unusual thickenings or lumps. Cancer is one of the most hazardous public health problems nowadays. According to the data of International Agency for Research on Cancer, more than 12.4 millions of new cancer cases, 7.6 millions of cancer-caused deaths, and 28 millions of cancer survivors were registered in 2008 worldwide (Jemal et al., 2010, 2011; Siegel et al., 2012). About half of cancer cases and two-thirds of cancer deaths occur in low- and middle-income countries (Jemal et al., 2010, 2011; El-Basmy et al., 2012; Kutikhin et al., 2012a; Zhivotovskiy et al., 2012; Baade et al., 2013; Krishnan et al., 2013; Krishna Rao et al., 2013; Moore, 2013; Pandey and Chandravati, 2013; Perez-Santos and Anaya-Ruiz, 2013; Zhang, 2013). Despite this scary statistics, annual death rates have been decreasing gradually since 1990 in men and since 1991 in women (Jemal et al., 2011). This progress is largely as a result of intensive development of modern preventative measures against cancer, the efficacy of which is growing every year. Obviously, prevention of a disease is much easier than its treatment, and so the problem of cancer prevention is one of the most basic issues when combating the burden of the disease. Carcinogenesis is a sophisticated multistep process of initiation, development, and progression of cancer. The key feature of this process is that it leads to a fundamental reorganization of the normal cells of the body. The occurrence of cancer is associated with an impaired proliferation and differentiation of cells due to genetic alterations. One of the most common genetic alterations is a mutation. In order to provoke cancer, the mutation must occur in a specific gene, called proto-oncogene. The proto-oncogenes are a class of genes that encode proteins and enzymes involved in the regulation of cell cycle, as well as cell differentiation, and proliferation. The proto-oncogenes are often engaged in multiple signal transduction pathways of mitosis regulation; hence, their proper functioning is extremely important for the normal cell development and homeostasis. It is important to underline that the proto-oncogenes are entirely normal genes, but occasionally they may initiate cancer development due to acquisition of genetic alterations within their structure. A single error in the proto-oncogene converts it to the oncogene, which is able to give rise to the malignant transformation (Weinberg, 2007). The oncogene is characterized as a proto-oncogene expressed at inappropriate (i.e., significantly high) levels. As a consequence, excessively high expression of the oncogene leads to an increase in protein expression and stability of its mRNA. This, in turn, alters numerous metabolic processes within a cell and ultimately results in cancer development. Currently, oncogenes are regarded as a broad class of genes that includes numerous transcription factors, receptor or cytoplasmic tyrosine kinases, mitogens, growth factors, and GTPases (Weinberg and Robert, 2007). Apart from carcinogenesis itself, other important points we should mention are cancer risk factors and individual cancer susceptibility. A risk factor is a chance that a person will have a disease or recurrence. Some do not get cancer. Some do, and we have nothing to do with that. Why do not we all develop this disease? What is the lifetime risk for getting cancer or dying from cancer? These questions have been investigated for decades as hundreds and thousands of epidemiological studies were performed. Large-scale investigations of cancer incidence and mortality revealed that the risk of getting this disease is largely due to the possession of specific risk factors. In other words, this means any risky behavior that might provoke massive damage to genome, thereby initiating malignant transformation. So far, a huge number of factors determining the likelihood of acquiring cancer throughout life have been established. Most of them include lifestyle factors, such as excessive alcohol consumption, tobacco smoking, overweight and obesity, and lack of physical activity, and unhealthy diet (Weinberg and Robert, 2007). The above-mentioned factors are common for all malignancies; however, some types of cancer have their own risk factors. For example, prolonged exposure to UV rays and getting multiple sunburns greatly increase skin cancer risk (de Gruijl, 1999; Dummer and Maier, 2002; Rigel, 2002). The other case in the point is that long-term estrogen therapy is associated with an increased risk of breast cancer in postmenopausal women (Lumachi et al., 2011; Rozenberg et al., 2013; Williams and Lin, 2013). According to recent research, even blood group is to be considered as a risk factor for certain cancers (Xie et al., 2010; Khalili et al., 2011; Yuzhalin and Kutikhin, 2012a; Liumbruno and Franchini, 2013). Of course, possessing a particular risk factor does not mean that a person will definitely get a disease. On the other hand, not having any risk factors does not guarantee total absence of cancer throughout life. But one thing is certain—the accumulation of risk factors is directly proportional to the probability of the occurrence of the disease. The good thing about lifestyle factors is that they can be easily avoided, i.e., can be controlled. We can give up with pernicious habits and lead a healthy life to live without illnesses. It is estimated that up to 40% of cancers could be prevented by lifestyle changes. However, we are unfortunately not able to change our genetic predisposition to cancer. Due to differences in our genomes, some individuals are especially prone to malignant transformation and at first glance there is nothing we can do about it. However, it is well known that early defined, most of the cancers have a good cure rate. Therefore, early prevention and diagnosis based on genetic counseling are the most basic issues when combating the burden of the disease (Yuzhalin and Kutikhin, 2012b). The Human Genome Project has laid the groundwork for the understanding of the roles of genes and their inherited variations (especially single nucleotide polymorphisms) in the etiopathogenesis of cancer (Sachidanandam et al., 2001; Tsigris et al., 2007; Yuzhalin, 2011; Yuzhalin and Kutikhin, 2012c,d,e; Kutikhin and Yuzhalin, 2012a,b,c; Kutikhin et al., 2014). Importantly, some examples of personalized cancer management are applicable even today. For instance, testing for mutations involved in the development of familial breast and ovarian cancer prompts individualized prophylactic therapy including mastectomy and oophorectomy (Wang et al., 2012). Yet another uncontrollable risk factor for cancer is age. Moreover, growing older is the biggest risk factor for developing tumors. It is well known that cancer is primarily a disease of older people, and incidence rates increase with age for most malignancies. During the twentieth century, a dramatic increase in average life expectancy has been observed; therefore, even 100 years ago the problem of cancer was not as acute as it is today. Longer lifespan is essentially associated with a higher number of accumulated mutations within the genome, which in turn increases the share of mutations within the proto-oncogenes. Much research is being performed to investigate mediators that are supposed to connect cancer and aging. For example, tumor suppressor protein p53 has a considerable influence on both general aging and cancer development; currently, multiple therapeutic approaches are being developed to ameliorate or delay aging and simultaneously prevent tumor formation (reviewed by Hasty and Christy, 2013). It is important to note that carcinogenic mutations as well as all other mutations are caused by a wide range of substances called carcinogens. All known mechanisms of human tumorigenesis may be divided into three main groups, namely, physical, chemical, and biological. So far, many important features of carcinogenesis are not well understood and therefore we here give only a brief insight on the existing knowledge about carcinogens and their types. Physical carcinogens are extremely variable in their nature and sources. The term “physical carcinogen” includes the following agents: ionizing radiation (all types, including X-rays, γ rays, neutrons, radon gas, and UV light), leather dust, talc, coal soot, wood dust, asbestos, erionite, and other natural and man-made mineral fibers and respirable dusts (Maltoni et al., 2000). Plenty of experiments on mice models demonstrated that dusts and fibers cause cancer when inhaled for a long time. It was also revealed that intratissue implantations of hard and soft metallic or synthetic materials in the form of films, disks, squares, and foams are associated with cancer development as well (Maltoni et al., 1980; Maltoni and Sinibaldi, 1982). In addition, numerous nonfibrous particulate materials, such as crystalline silica and metallic nickel, are also regarded as carcinogens (Hueper, 1955). The mechanisms of physical carcinogenesis are well studied. Physical carcinogens are believed to have a nonspecific irritative effect on cells, which significantly violates various metabolic processes and leads to an excessive DNA damage, which results in cancer development. Generally, physical carcinogens require many years of exposure after getting inside the body to develop cancer. It has been long discovered that lung cancer is fairly frequent among industrial workers who are exposed to prolonged inhalation of asbestos, talc, or coal soot (Falk and Jurgelski, 1979; Wild, 2006; Lenters et al., 2011). With regard to radiation, it is well known that UV rays directly damage cell DNA and therefore are responsible for most cases of skin cancer. Regular use of tanning lamps and prolonged indoor tanning have long been established as important risk factors for skin cancer (Narayanan et al., 2010). The list of the most common physical carcinogens is represented in Table 1.1. Table 1.1. Physical Carcinogens According to the International Agency for Research on Cancer List Siemiatycki et al. (2004). Chemical carcinogenesis is characterized by the modification of the molecular structure of the DNA by various chemical compounds. Importantly, chemical carcinogens are responsible for about 80–90% of all human cancers. The most evident example of chemical carcinogenesis is the association between smoking and lung cancer (Risser, 1996). Virtually all the chemical carcinogens are ubiquitous, i.e., they can be found in the general environment, like prepared food, tobacco smoke, engine exhausts, paints, alcoholic beverages, etc. Some of the chemical carcinogens are regarded as occupational carcinogens, i.e., they can be found in specific work locations only. Importantly, many chemical substances are not carcinogenic themselves, but they convert to the carcinogenic products within the body; therefore, they are termed procarcinogens. It is interesting to note that cancer may also be initiated by the metabolism of endogenous chemicals as well. For example, products of lipid peroxidation and estrogens are known to produce DNA adducts as well as excessive DNA damage (Chung et al., 1996; Bolton et al., 1998). Table 1.2 includes the list of the most dangerous chemical carcinogens. Table 1.2. Some Chemical Carcinogens According to the International Agency for Research on Cancer List Siemiatycki et al. (2004). Biological carcinogenesis is referred to as a cancer that is driven by infectious agents, such as viruses, bacteria, fungi, protozoa, and helminths. As compared to previous mechanisms, biological carcinogenesis is the least studied, and numerous discrepancies may be found in the current literature on this issue. Biological carcinogenesis is the most curious one, and we will describe this in more detail. So far, the four main mechanisms of biological carcinogenesis can be proposed. Viral mechanisms The phenomenon of viral carcinogenesis is remarkable. The point is that in very rare cases malignant transformation could be induced by so-called oncogenic viruses, which carry oncogenes in their own genome. Integration of the viral genome into the host chromosome is followed up by multiple transcription and translation of viral genes, including oncogenes (Weinberg and Robert, 2007). Nowadays, more than 12% of human cancers can be attributed to a viral infection (Carrillo-Infante et al., 2007). For instance, the association between human papillomavirus and cervical cancer has long been established. In extremely rare cases, viruses possessing no oncogenes in their structure may promote cancer by inserting their genome adjacent to cellular proto-oncogenes, thereby causing their expression. Due to the fact that in this case viral genome insertion is not specific and requires more time to get near the oncogene, these viruses are called slowly transforming viruses (Weinberg and Robert, 2007). Immune mechanisms It is well known that chronic inflammation caused by infectious agents greatly increases the risk of cancer occurrence in the surrounding cells. In particular, inflammation induces mutations and epigenetic alterations by means of the formation of free radicals and DNA damage, inhibition of apoptosis, and promotion of cell proliferation (Kutikhin et al., 2013). This type of mechanisms is possessed by virtually all the known biological carcinogens. In this regard, an excellent example is the Helicobacter pylori infection, which is a major cause of gastric cancer (Pritchard and Crabtree, 2006). Furthermore, the parasite-driven modulation of the host immune response may sometimes lead to the deregulation of tumor immune surveillance, thereby increasing risk of malignant tumor formation. Metabolic mechanisms There is accumulating evidence that infectious agents may participate in modification, degradation, biotransformation, and detoxification of chemical compounds entering the gastrointestinal tract after consumption of food and drink eventually metabolizing them to chemical carcinogens. Numerous representatives of gut and oral microbiota have shown these activities in multiple studies (Kutikhin et al., 2012b, 2013). Additionally, human gastrointestinal microbiota can also have an influence on weight gain and promote obesity hence elevating the risk of obesity-associated cancers (Robles Alonso and Guarner, 2013). Toxin-mediated mechanisms Certain bacteria and protozoa are able to produce toxins that are contained in their cell wall. Some of the toxins were demonstrated to possess carcinogenic activity by violating cell–cell interactions, proliferation, intracellular signal transduction, and cell growth and differentiation (Kutikhin et al., 2012b, 2013). In addition, several toxins were found to induce resistance to multiple mechanisms of apoptosis, thereby contributing to cancer development as well. An established tumor violates various metabolic processes within the cell and acquires partial independence from the regulatory systems of the body. The organism tries to get rid of cancer cells by means of immune response, which is not always effective. The cohesion between cancer cells is low, and therefore the development of a tumor is accompanied by the penetration of some cancer cells through the blood vessels, and the consequent spread of these cells to the other locations in the body (Weinberg and Robert, 2007). This leads to the generation of new malignancies termed metastatic tumors. Cancers develop progressively, and metastatic cancer is the terminal stage of tumor growth. The most common metastasis locations are the liver, lungs, brain, and bones (Bacac and Stamenkovic, 2008). A spread of metastases greatly decreases a patient’s chance of survival; hence, most cancer deaths nowadays are due to malignancies that have spread from their primary site to other organs.1.1 A Brief Overview of Cancer Phenomenon
1.1.1 What is Cancer?
1.1.2 Cancer Statistics
1.1.3 Carcinogenesis and Cancer Risk
1.1.4 General Mechanisms of Carcinogenesis
•
Carcinogen Source Associated Cancer Type Arsenic Nonferrous metal smelting, electrical and semiconductor devices Lung, skin, liver Asbestos Asbestos industry, fire-resistant textiles Lung, larynx Beryllium Aircraft and aerospace industry, nuclear reactors Lung Cadmium Various dyes and pigments, batteries, industrial paints, metal coatings Lung Chromium Steel and copper alloys, tanning agent, magnetic tape coatings, abrasive, refractory materials Lung Diesel particulate matter (ash particulates, metallic abrasion particles, silicates) Diesel engines’ exhaust Lung, bladder Erionite Sewage and agricultural waste. Used in waste treatment and in air pollution control systems Mesothelium Ionizing radiation Ubiquitous. Risk occupations are radiologists, nuclear workers, underground miners, plutonium workers Blood, bone, lung Nickel Nickel smelting and refining Lung Silica and crystalline Granite, ceramics, and stone industries Lung Talc Manufacture of cosmetics, pottery, paper Mesothelium, lung Wood dust Wood industry Nasal cavity Carcinogen Sources Associated Cancer Type Aflatoxin Food industry Liver Aromatic amine dyes Dye and pigment industry Bladder Benzene Light fuel oil, solvents, rubber, printing industry Blood Coal tars and pitches Production of refined chemicals Skin Ethylene oxide Rocket propellant, ripening agent for crops Blood Isopropylalcohol Fuel additives, medical disinfecting pads, solvents Nasal cavity Mustard gas Military forces Lung, larynx, pharynx Polycyclic aromatic hydrocarbons Atmospheric pollutants, cooked food All sites Tetrachlorodibenzo-para-dioxin Waste incineration, paper bleaching All sites Components of tobacco smoke (>30) Tobacco Lung Vinyl chloride Refrigerant Liver •
1.1.5 Further Cancer Development
URL:
https://www.sciencedirect.com/science/article/pii/B9780128011218000014
Cancer is the uncontrolled growth and development of cells in the body, and is one of the foremost reasons of deaths throughout the world. There are over 100 different types of cancers that are categorized on the basis of the affected tissue or organ of the human body. Cancer, a multifactorial malady involves multifarious changes in the genome due to interactions with the individual’s environment. The hallmarks of the cancer are uninhibited replication, inability to respond to growth signals, resulting in arrest of the cell division, continuous angiogenesis, resistance to apoptosis, and the ability to infiltrate other tissues. Currently, cancers can be cured by means of both conventional tonic approaches, i.e., surgery, radiation therapy and chemotherapy, and nonconventional or complementary therapeutic methods, including hormone therapy, immunotherapy, nanotherapy, etc. These well-established therapeutic interventions specifically target the tumors and either inhibit or slow down the growth rate of cells, but incompetent to completely provide protection. Nevertheless, these existing cancer cure practices cause adverse side effects, and largely distress the normal cells, tissues, and organs. Selecting the best cancer therapy approach depends on various factors, such as the type of malignancies, growth stages, age, management frequencies, dosage of medicines, and healthiness of patients. More recently, various molecular-based approaches are being increasingly researched, including gene therapy, targeted silencing by siRNAs, the expression of genes triggering apoptosis and wild tumor suppressors. This chapter discusses about the cancer biology and various conventional and modern treatment approaches to combat diverse forms of cancer.Abstract
URL:
https://www.sciencedirect.com/science/article/pii/B9780323909518000102