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Multiple Myeloma

Acknowledgments Dr. G. Tonon acknowledges the support from the Associazione Italiana per la Ricerca sul Cancro (AIRC), the Association for International Cancer Research (AICR), and the Cariplo Foundation and is a recipient of a Marie Curie International Reintegration Grant. Dr. K. C. Anderson is an American Cancer Society Clinical Research Professor. Multiple myeloma (MM) is a hematological cancer characterized by the accumulation of neoplastic plasma cells…

Lymphoma

The lymphoid malignancies comprise one of the most diverse and heterogeneous sets of diseases that exist under a single type of malignancy. In 2012, the American Cancer Society estimated there were about 70,000 cases of non-Hodgkin lymphoma (NHL), and about 10,000 cases of Hodgkin lymphoma in the United States, collectively accounting for about 4% to 5% of all cancers. The estimated number of U.S. cancer deaths…

Biology of Adult Myelocytic Leukemia and Myelodysplasia

Introduction The genesis of human myeloid leukemia involves the deregulation of the differentiation and maturation programs of the hematopoietic myeloid lineage that originates from primitive stem cells with multilineage potential. Myeloid leukemias have been linked to the acquisition of chromosomal aberrations and/or somatic mutations that result in subversion of the proliferation, differentiation, and survival cellular programs. Historically, the different acute myeloid leukemia (AML) phenotypes have been…

Molecular Biology of Childhood Neoplasms

Cancer is the most common cause of disease-related death in children beyond the newborn period. Although childhood cancers, as a group, account for only a small proportion of all human cancer, their unique biologic features, cell of origin, and response to therapy make them intriguing models with which to study and understand the process of human carcinogenesis. Although most childhood cancers occur sporadically and their etiology…

Molecular Genetics of Acute Lymphoblastic Leukemia

Introduction Acute lymphoblastic leukemia (ALL) is a sharply contrasting disease in the pediatric and adult populations. In children, it is both the most common leukemia and the most common malignancy. Childhood ALL has been emblematic of medical progress, with steady improvement over the past 50 years and a current 5-year event-free survival (EFS) rate of over 85% ( Figure 26-1 ). In contrast, in adults, ALL…

High-Content Analysis with Cellular and Tissue Systems Biology: A Bridge between Cancer Cell Biology and Tissue-Based Diagnostics

Acknowledgments This work was supported in part from research grants from the State of Pennsylvania Tobacco Funds (DLT), NIH R01 GM075205IH (RFM), NIH-NIGMS R01 GM086238 (TL, Ivet Bahar, PI), NIH-NCRR UL1RR024153-05 (TL and JRF, Steve Reiss, PI), and NIH-NCI 1R21CA164433-01A1 (CC, Liu, PI), and Pennsylvania Department of Health Cure Program Grant RFA#10-07-03 (RC-T). The authors thank Andy Stern for discussions on cancer biology and drug discovery,…

Understanding and Using Information about Cancer Genomes

High-resolution genome analysis techniques are now being used in international cancer genome analysis efforts to catalog aberrations driving the pathophysiology of nearly all major cancer types. The Cancer Genome Atlas (TCGA, ) project and the International Cancer Genome Consortium (ICGC, ) represent the largest of these. The TCGA project is assessing aberrations in 500 to 1000 tumors from each of about 20 major human…

The Technology of Analyzing Nucleic Acids in Cancer

Introduction to Next-Generation Sequencing Current DNA sequencing methods differ dramatically from a mere 7 years ago, when next-generation sequencing (NGS) instrumentation was first introduced. Indeed, the science of DNA sequencing is only 35 years old, and its companion discipline known as genomics has been revolutionized by the advent of NGS instrumentation and its application to myriad biological questions. Whereas conventional DNA cloning and sequencing approaches, largely…

Protein Biomarkers for Detecting Cancer: Molecular Screening

Biomarkers of early cancer detection, specific markers of a malignancy type, and predictive markers of response to treatment will aid in the early diagnosis and selection of the most efficient therapies. An exponential growth in technologies has been achieved toward this goal in the past decade. However, it is safe to say that the field of disease biomarkers produced many more publications on the subject than…

Biomarkers for Assessing Risk of Cancer

Cancer is a complex disease involving both environmental and genetic determinants. The majority of cancers are caused by environmental and lifestyle factors, including smoking, alcohol use, infectious agents, occupation, diet, obesity, and lack of physical activity. However, only a small number of cancers, such as lung cancer (smoking) and cervical cancer (human papillomavirus [HPV] infection), have a major environmental risk factor that accounts for the bulk…

Cancer Systems Biology: The Future

Over the past decade, complementary and at times antithetic views of tumor initiation and progression have emerged, often based on the introduction of novel high-throughput technologies for the characterization of the cell’s genetic and epigenetic landscape. On the one hand, the availability of a comprehensive map of the human genome has allowed the development of gene expression profiling techniques, mostly microarray based, to monitor the dynamic…

Inflammation and Cancer

Introduction Adult tissues contain a multitude of cell types that are spatially and functionally coordinated to regulate normal tissue homeostasis. When a tissue becomes injured, for example, from a skin wound, there is a surge of infiltrating cell types and inflammatory responses within the microenvironment that work in concert to heal the injury and restore tissue homeostasis. Interestingly, tumors share many features with injured tissue, as…

Invasion and Metastasis

In the written history of medicine, neoplasms have been diagnosed for nearly 4000 years. Almost from the beginning, medical practitioners recognized that the most life-threatening attribute of neoplastic cells is the ability to disseminate and colonize distant tissues. When tumors are diagnosed and have not spread beyond the tissue of origin, cure rates for most cancers approach 100%. However, when tumor cells have established colonies elsewhere,…

Tumor Angiogenesis

Solid tumors require a vascular system to grow beyond about 2 mm in diameter, a size at which diffusion of oxygen and nutrients is limiting. The establishment of a tumor vasculature through the process of angiogenesis overcomes these limitations, while also providing a conduit through which cancer cells can metastasize. The close association between tumor growth and increased vascularity was described in the 19th century by…

The Role of the Microenvironment in Tumor Initiation, Progression, and Metastasis

Acknowledgements The authors are grateful to Ms. Negest Williams for unparalleled administrative support. The discovery in the 1970s of proto-oncogenes, genes that become oncogenic (“cancer causing”) either through genetic modifications or increased expression, and tumor suppressor genes, those that if expressed at the right levels would suppress progression to malignancy, spurred a revolution. Given the excitement and the implication of these discoveries, it may not be…

Cellular Senescence

The term senescence was coined more than 50 years ago to describe the loss of replicative capacity of normal human diploid cells in culture. At that time, senescence was proposed to generally reflect the process of cellular aging. Early studies also noted differences between the propensity of normal and malignant cells to senesce, with malignant cells being frequently “immortalized” or capable of unlimited subcultivation in vitro.…

Apoptosis, Necrosis, and Autophagy

In the simple arithmetic of life, a tissue grows if cells divide more frequently than they die, whereas one in which cell death is more frequent than cell division shrinks. This arithmetic, trivial as it seems, is at the heart of the understanding of cancer and the efforts to effectively treat it. However, the mechanisms that control this relationship are far from trivial. One theory of…

The Metabolism of Cell Growth and Proliferation

Why Is Metabolism Important to an Understanding of Cancer? At its heart, cancer is a disease of abnormal proliferation. Proliferation represents a distinct metabolic challenge: cells must replicate all of their proteins, lipids, and nucleic acids to generate a daughter cell. This process requires vast inputs of energy and raw materials. As a result, proliferating cells take up large quantities of nutrients in order to engage…

Cell Growth

What Is Cell Growth? Cell growth is the process by which cells accumulate mass and increase in physical size. On average, dividing animal cells are approximately 10 to 20 μm in diameter. Terminally differentiated cells have a wide range of sizes, spanning from tiny red blood cells (∼5 μm in diameter) to motor neurons, which can grow to hundreds of micrometers in length. For a typical…

Regulation of the Cell Cycle

Basic Principles of Cell Cycle Progression The essential function of cell cycle control is the regulated duplication of the cells’ genetic blueprint and the division of this genetic material such that one copy is provided to each daughter cell following division. The cell cycle can be divided conceptually into four individual phases. The “business” phases include S phase or synthesis phase, which is the period during…