Molecular Biology, Genetics, and Translational Models of Human Cancer

Abstract

Overview Cancer is a disease of abnormal cellular behavior and characterized by molecular aberrations that promote cellular proliferation and survival. Neoplastic progression ultimately produces tumor masses that compromise local organ function, and the invasion and metastasis of malignant cells away from their tissue of origin and spread throughout the body cause a diverse array of pathophysiologic sequelae that compromise the quality and length of life of patients. A background knowledge of cancer pathogenesis and cancer models should help oncologists understand the developing approaches for optimal patient care, including the new concept of personalized medicine. This article is a basic, “methods‐oriented” survey of molecular biology directed toward the clinician or trainee who wants a fundamental understanding of this discipline. It describes the principles that underlie the procedures used most commonly by molecular biologists and provides examples of clinically relevant situations that draw on particular techniques. Molecular biology already plays an important role in clinical cancer medicine, both in terms of diagnosis (e.g., in the analysis of tumors for prognostic or pathogenetic information) and in treatment (e.g., in the production of pharmacologic and biologic agents, such as recombinant growth factors and monoclonal antibodies). We will begin with an overview of genes, gene expression, and gene cloning. Our discussion of techniques will follow the flow of genetic information as we explain the procedures used to analyze gene expression at the levels of DNA, ribonucleic acid ( RNA ), and protein. We conclude with a discussion of current cancer modeling systems in vitro and in vivo . Good general overviews of these topics can be found in several books. 1–3