It is my intention to update the several teaching documents at this website, beginning now with Neoplasia. The goal is to focus on newer insights into the molecular biology of cancer, namely, the somatic gene mutations and molecular pathways that underlie human cancer and contribute to the potential development of molecular targets for cancer adjuvant (post-surgical/radiation) therapy.

Historically, the seminal idea that somatic gene mutation and activation may contribute to cancer development dates back many decades ago to the observations and publications of Boveri (Boveri, T., The Origin of Malignant Tumors, 1929, Williams & Wilkins). However, available techniques in cell biology did not exist for further investigation at that early time, and future advances awaited the onset of the “modern” era of cytogenetics (perhaps the `mid 50s') with improved methods of cell culture, slide preparation, chromosome banding, proof that the normal human diploid cell chromosome number was 46, not 48 as long held, and recognition of distinctive karyotypes in some forms of cancer (Nowell, P., & Hungerford, D., J. Natl. Cancer Inst, 25, 85 (1960); Rowley, J.D., Nature 243, 290-293 (1973).

Next to consider are the “hallmarks of cancer” (Hanahan, D., & Weinberg, R.A., Cell 100, 57-70 (2000), among them, the intrinsic capacity of neoplastic cells to initiate and sustain cell growth and proliferation; to resist cell signals that normally inhibit cell division or that promote cell maturation (differentiation); the presence and function of cancer stem cells; the many interacting factors that contribute to tumor initiation, progression, invasion, recurrence, metastasis, and new blood-vessel formation (angiogenesis).

Cancer of common clinical presentation is a somatic genetic disease (Nurse, P., Nature Med 4, 1103-04 (1998). As previously noted (Neoplasia /Carcinognesis), the development of cancer is a multi-factorial process, one that involves both genetic and environmental (biological, chemical, physical) damage to somatic cell DNA and is manifest by sequential somatic gene mutation and expression, with interaction of the encoded protein/peptide products with those of other cancer-related genes, among them: oncogenes, tumor suppressor genes, DNA nucleotide mismatch repair genes, and genes that mediate programmed cell death (apoptosis) for cells that  fail to have DNA mismatch repair. The cytogenetic manifestations of somatic gene mutation in a variety of human cancers include: genetic rearrangement (chromosomal translocation), gene amplification, gene deletion, point (single base) mutation, and promoter insertion.

Some of the protein/peptide products of mutant genes function as stimulatory growth signals that pass from cell to cell and along transmembrane pathways through the cell membrane to the nucleus where they mediate interaction among growth factors, growth-factor receptors, post-receptor regulatory proteins, and nuclear controls (mitogenic kinases) that regulate or drive progression through the cell division cycle.

Research in the molecular biology of cancer has led to the identification of some molecular targets with applications in cancer (adjuvant) therapy. This concept also dates back many decades ago with the recognition that natural gonadal hormones can stimulate the growth of certain forms of human cancer, such as estrogen-dependent breast cancer or androgen-dependent prostate cancer, and that gonadectomy or appropriate inhibition of the stimulating hormone can slow the growth and progression of a responsive cancer.

The concept that tumors secrete proangiogenesis growth factors that can promote the vascular development and growth of solid tumors was set forth by Folkman who in 1971 (Folkman, J., N Eng J Med. 1971; 285:1182-1186) postulated that inhibiting this process of angiogenesis might provide an approach to cancer therapy (Folkman, J., Nat Med. 1995; 1:27-31).

Since numerous genes and signaling pathways contribute to cancer initiation, development and control, many analytical techniques applicable to freshly frozen tissue specimens are now available in major cancer centers for determining gene expression profiles by DNA microassay analysis, appropriate messenger RNA expression, and presence and in situ location of protein/enzyme molecular targets of therapy (Kononen, J., et al., Nature Med 4, 844-847 (1998).

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TABLE 1. Short Introductory List of Molecular Targets of Cancer Therapy

Some Additional Molecular Targets of Cancer Therapy

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