Cancer Cell Biology The treatment of most human cancers with conventional cytoreductive agents has been unsuccessful due to the Gompertzian-like growth kinetics of solid tumors (., tumor growth is exponential in small tumors, with increasing doubling times as tumors expand; since conventional chemotherapeutic agents target proliferating cells, noncycling cells in large tumors are relatively resistant). Genetic instability is inherent in most cancer cells and predisposes to the development of intrinsic and acquired drug resistance. Thus, although tumors arise from a single cell (., they are clonal), large tumors become very heterogeneous with multiple related subclones, some of which will. | Chapter 080. Cancer Cell Biology and Angiogenesis Part 2 Cancer Cell Biology The treatment of most human cancers with conventional cytoreductive agents has been unsuccessful due to the Gompertzian-like growth kinetics of solid tumors . tumor growth is exponential in small tumors with increasing doubling times as tumors expand since conventional chemotherapeutic agents target proliferating cells noncycling cells in large tumors are relatively resistant . Genetic instability is inherent in most cancer cells and predisposes to the development of intrinsic and acquired drug resistance. Thus although tumors arise from a single cell . they are clonal large tumors become very heterogeneous with multiple related subclones some of which will be resistant to specific therapies leading to the selection of progressively more resistant tumors as treatment progresses. Since a 1-cm tumor often contains 109 cells and patients typically present to their physicians with 101O-1011 tumor cells the obstacle to curative treatment becomes more understandable. Rationally designed targetbased therapeutic agents directed against the specific molecular derangements that distinguish malignant from nonmalignant cells have become possible with advances in the understanding of oncogene and tumor-suppressor pathways. This chapter describes the convergence of scientific pharmacologic and medical knowledge that has led to the targeted therapy of cancer. Therapeutic Approaches to Cell Cycle Abnormalities in Cancer The mechanism of cell division is substantially the same in all dividing cells and has been conserved throughout evolution. The process assures that the cell accurately duplicates its contents especially its chromosomes. The cell cycle is divided into four phases. During M-phase the replicated chromosomes are separated and packaged into two new nuclei by mitosis and the cytoplasm is divided between the two daughter cells by cytokinesis. The other three phases of the cell cycle are .
