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Imaging

Summary of Key Points Noninvasive medical imaging often is essential to cancer management at multiple times in the course of the illness. Imaging currently is used for screening to detect cancer, characterizing lesions, performing locoregional and systemic staging, providing prognostic information, assessing response during and after therapy, restaging after treatment, performing follow-up of patients for recurrence, and precisely guiding biopsies and therapies such as external beam…

Pathology, Biomarkers, and Molecular Diagnostics

Summary of Key Points Biomarker development has profoundly affected basic understanding of carcinogenesis and expanded means of intervention in human cancers. Biomarkers have been applied with variable success in three broad areas that correspond to phases of tumor development and progression: (1) early detection, (2) diagnosis, and (3) prediction of clinical outcome (prognosis) and response to targeted treatment. For early detection, biomarkers go through five stages…

Genetic and Epigenetic Alterations in Cancer

Summary of Key Points A root cause of cancer is the accumulation of genetic and epigenetic defects in key cellular pathways regulating proliferation, differentiation, and death. The defects in cancer cells are of two types: gain-of-function alterations affecting oncogenes, and loss-of-function alterations affecting tumor suppressor genes. Regardless of whether the defects are genetic or epigenetic in nature, a common net consequence is dysregulation of gene expression…

Genetic Factors: Hereditary Cancer Predisposition Syndromes

Summary of Key Points The discovery of inherited mutations of genes associated with increased risk for cancer provides important clinical opportunities for early detection and prevention of common and rare forms of human malignancies. Syndromes of cancer predisposition often involve multiple organ systems, affect paired organs with bilateral or multifocal tumors, and have onset at an earlier age compared with nonfamilial tumors. The diagnosis of particular…

Viruses and Human Cancer

Summary of Key Points More than 15% of human cancers are known today to be caused by viruses. A hallmark of virally induced cancers is that they are associated with persistent viral infections. Although some viruses encode oncogenes that directly contribute to the cancers they cause, other viruses are thought to result in cancer indirectly by causing chronic destruction of the target organ from which the…

DNA Damage Response Pathways and Cancer

Summary of Key Points DNA repair and the cellular response to DNA damage are critical for maintaining genomic stability. Defects in DNA repair or the response to DNA damage encountered from endogenous or external sources results in an increased rate of genetic mutations, often leading to the development of cancer. Inherited mutations in DNA damage response pathway genes often result in cancer susceptibility. The major active…

Environmental Factors

Summary of Key Points Current Concepts in Carcinogenesis A key paradigm in environmental carcinogenesis—that of gene-environment interactions, a concept used to describe the complex interplay between individual or population genetics and responses to chemical agents—has undergone an expansive transformation into a more contemporary understanding of the human “exposome.” The exposome is the cumulative lifelong burden of disease-contributing stressors, including exogenous and endogenous agents of all types,…

Cancer Metabolism

Summary of Key Points Metabolism supports biosynthesis, energetics, and cell signaling including chromatin state and epigenetics. A common feature of each element of malignancy is the necessity to adapt metabolic functions. Altered metabolism in key metabolic pathways and networks is being exploited clinically for diagnostics and therapeutics. Old and new therapies target cancer metabolism, and the repurposing of metabolic drugs for cancer therapy is attractive and…

Tumor Microenvironment: Vascular and Extravascular Compartment

Summary of Key Points A solid tumor is an organ composed of neoplastic cells and stromal cells including immune cells nourished by vasculature made of endothelial cells—all embedded in an extracellular matrix. The interactions among these cells, their surrounding matrix, and their local microenvironment control the expression of various genes. The products encoded by these genes, in turn, control the pathophysiologic characteristics of the tumor. Tumor…

Stem Cells, Cell Differentiation, and Cancer

Summary of Key Points Many tumors originate in organs and tissues that undergo a continuous process of cell turnover, which is sustained by a minority population of stem cells (e.g., the colon, breast, lung, prostate, brain, and bone marrow). Stem cells have four fundamental properties: the ability to give rise to new stem cells with intact and unlimited growth potential (self-renewal), the ability to give rise…

Cancer Immunology

Summary of Key Points Cancer is characterized by genetic and epigenetic instability leading to both unique and sometimes common mutations and “ectopic” overexpression of genes not normally expressed in the tissue of origin. Cancer-specific proteins arising as a result of genetic mutations appear to provide the most potent antigens visible to the T-cell arm of the immune system. Because the number of cancer-specific antigens expressed varies…

Pathophysiology of Cancer Cell Death

Summary of Key Points Regulated cell death mainly occurs via extrinsic apoptosis, intrinsic apoptosis, necroptosis, and mitochondrial permeability transition (MPT)–driven regulated necrosis. Autophagy operates as a bona fide cell death mechanism in a few, mostly developmental, settings. Oncogenesis results from multiple molecular alterations, one of which frequently impairs the ability of cancer cells to die in response to exogenous or endogenous signals. Several oncoproteins and oncosuppressor…

Control of the Cell Cycle

Summary of Key Points Most cells in postnatal tissues are quiescent. Exceptions include abundant cells of the hematopoietic system, skin, and gastrointestinal mucosa, as well as other minor progenitor populations in other tissues. Many quiescent cells can reenter into the cell cycle with the appropriate stimuli, and the control of this process is essential for tissue homeostasis. The key challenges for proliferating cells are to make…

Cellular Microenvironment and Metastases

Summary of Key Points Metastases are responsible for more than 90% of all cancer-related deaths. Gene dysregulation, the tumor microenvironment, and host cells drive the metastatic spread of tumor cells. Metastasis can be subdivided into invasion and migration from the primary tumor; intravasation into the vasculature; dissemination and survival in the circulation; extravasation from the vasculature; survival and metabolic adaptation in the distant tissue; dormancy; and…

Intracellular Signaling

Summary of Key Points Ligand binding and activation of cell surface and internal receptors trigger the activation and/or suppression of signaling cascades that regulate diverse cellular processes including cell growth, proliferation, survival, and invasion, among others. Multiple nodes within these intracellular signaling networks are genetically and epigenetically altered in human cancers, leading to constitutive pathway activation or suppression. Some cancers are dependent on genomic alterations in…

Molecular Tools in Cancer Research

Summary of Key Points Our understanding and treatment of cancer have always relied heavily on parallel developments in biologic research. Molecular biology provides the basic tools to study genes involved with cancer growth patterns and tumor suppression. An advanced understanding of the molecular processes governing cell growth and differentiation has revolutionized the diagnosis, prognosis, and treatment of malignant disorders. This introductory chapter relates basic principles of…

Diagnostic Use of Venoms

The most common use of snake venom molecules as reagents in hemostasis is described below. Fibrinogen Assessment Fibrinogen promotes platelet aggregation and is converted to fibrin by thrombin, with formation of a hemostatic plug. Reptilase Time This is a modification of the thrombin time (TT) in which thrombin-like enzymes (serine proteases) replace thrombin. The most commonly used enzyme is Batroxobin, a 43 Kda protein from the…

Thrombin Generation Assays

The TGA is a global test of coagulation systems, with the potential to contribute to the current arsenal of clinical prognostication and drug monitoring tools. By varying the conditions under which it is applied, the test can be made sensitive to virtually every known component of the clotting cascade. The current iterations of the test utilize a fluorogenic substrate to monitor thrombin generation beyond the time…

Circulating Microparticles

Microparticle (MP) analysis has become popular in the last decade because of mounting evidence of their active role in multiple cellular processes. Alterations in total MP numbers or changes in the relative abundance of MP populations have been correlated with multiple diseases. It is still unknown whether these MP alterations are markers of disease or whether MPs play an active role in the pathology, progression, or…