Milestones in Cancer Research: Discovering Oncogenes and Tumor Suppressor Genes

In 1911, Peyton Rous made a groundbreaking discovery when he found that the (Rous) sarcoma virus (RSV), an oncogenic virus, could induce cancer in chickens. Despite its significance, this finding took over fifty years to be acknowledged by the Nobel Committee, which finally recognized Rous in 1963, when he was eighty-four years old. Subsequent research revealed that RSV is a retrovirus containing RNA rather than DNA, which can be transcribed into DNA by the enzyme reverse transcriptase, present within the virus. The resulting abnormal DNA can integrate into the chromosomes of normal cells, altering their activity and leading to the development of cancer.

In 1976, Michael Bishop and Harold Varmus, based at the University of California, San Francisco, utilized RSV to demonstrate how normal cell genes can transform into malignant tumors. They identified specific regions of the viral genetic material, known as oncogenes, which can trigger the conversion of a normal cell into a cancer cell when influenced by other viral components, radiation, or certain chemicals. Remarkably, they found that the oncogene in RSV was not a viral gene, but rather a proto-oncogene derived from a normal cell, which the virus had acquired during replication within the host cell and carried along. Proto-oncogenes are responsible for encoding a kinase enzyme that initiates signals to stimulate normal cell growth and division. This groundbreaking discovery by Bishop and Varmus has led to the identification of numerous cellular genes that normally regulate growth and development but can become mutated, resulting in the formation of cancer.

Under normal circumstances, damaged DNA within genes is repaired or eliminated during the cell cycle. However, if these repair mechanisms are inadequate, mutations can accumulate, leading to genetic damage being passed on to the daughter cells. The development of cancer occurs when normal cells within the body undergo irreversible changes in their genetic material. Two types of genes, proto-oncogenes and tumor suppressor genes (TSG), play critical roles in regulating cell growth. Mutations in proto-oncogenes may result in excessive stimulation and uncontrolled cell growth, while mutations in TSG may disable the brakes that normally regulate cell growth.

In this image, Dr. Harold Varmus, renowned National Cancer Institute director and co-recipient of the 1989 Nobel Prize for his groundbreaking work on oncogenes and their role in cancer, delivers a presentation in 2010.

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