Part III: The Cancer Genome and Therapeutics
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Bishop begins his lecture with a historical review of the experiments that resulted in the realization that cancer has a genetic basis. He explains that mutations can cause normal cellular genes known as proto-oncogenes to become oncogenes, analogous to jammed accelerators causing uncontrolled cell division. Alternatively, mutations in tumor suppressor genes are analogous to a failed brake system. An accumulation of both types of mutation leads to the development of cancer.
In part 2 of his lecture, Bishop describes how the sequencing of cancer genomes will advance the study and management of cancer on various fronts, including the discovery of causes, the improvement of early detection, the prediction of outcome and the development of new therapeutics. He stresses the promise of designing therapeutics that can be targeted to those patients most likely to benefit from these drugs.
Bishop expands on this theme in part 3 where he describes experiments to find drugs that exploit vulnerabilities created by cancer genes, utilizing a genetic strategy known as “synthetic lethality.”
Dr. Bishop received his undergraduate degree from Gettysburg College and his M.D. from Harvard Medical School. Harvard provided Bishop with his first research experience and introduced him to the study of animal viruses. Bishop completed his clinical training at Massachusetts General Hospital and pursued a research fellowship at the National Institutes of Health. In 1968, he accepted a faculty position at the University of California, San Francisco and remains there to this day.
At UCSF, Bishop began to study Rous sarcoma virus. He was soon joined by Harold Varmus. Together, they made the seminal discovery that retroviruses can hijack genes that control normal cell growth and convert them to cancer causing oncogenes. Bishop and Varmus were honored with the 1989 Nobel Prize in Medicine or Physiology for this research.
Bishop served as chancellor of UCSF from 1998-2009. He is involved in many aspects of research advocacy and he continues to enjoy running his research lab and teaching students at UCSF.
- C. David Allis iBioSeminar: Epigenetics: Why Your DNA Isn’t Enough
- Mary Beckerle iBioSeminar: Adhesion, signaling and cancer
- J. Michael Bishop iBioMagazine: How I became a scientist
- David Botstein iBioSeminar: Fruits of the genome sequences for society
- Brian Drucker iBioSeminar: Imatanib (Gleevec) as a paradigm of targeted cancer therapies.
- Alfred Wittinghofer iBioSeminar: GTPase reactions and diseases
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Alberts, B. et al. "Cancer." Chapter 20 in Alberts, B. et al., The Molecular Biology of the Cell.
Stratton, M.R. "Exploring the genomes of cancer cells: progress and promise." Science 331:1553 (2011)
Hanahan, D. and Weinberg, R.A. "Hallmarks of cancer: the next generation." Cell 144:646 (2011)
Sawyers, C. "Targeted cancer therapy." Nature 432:294 (2004)
Kaehlin, W.G. Jr. "The concept of synthetic lethality in the context of anticancer therapy. Nature Reviews Cancer 5:689 (2005)"