How the Oncogene Opened the Door for Targeted Therapy

The second episode of Cancer: The Emperor of All Maladies, titled "The Blind Man and the Elephant," focused on some key discoveries made in the 20th century. One of those discoveries was of the human oncogene–a cancer causing gene.

“Science is a profession for manic-depressives…what drives one is one’s ongoing curiosity.”
— Robert Weinberg of MIT

Inspired during a walk one snowy Boston day, Dr. Robert Weinberg’s approach to find a human oncogene was beautifully simple: isolate individual genes from a human cancer cell, and then one by one, introduce each gene into a petri dish of normal cells. When the normal cells turn malignant, the oncogene would have been found.

It took a year, but Weinberg did discover the first human oncogene: Ras. It has since been learned that Ras has many subtypes, like HRAS and KRAS, which are significant in cancers such as lung, colorectal, bladder, and others. Treatment designed specifically around the presence of these oncogenes is now known as targeted therapy.

After Weinberg’s discovery of Ras, labs around the world worked to find more and more oncogenes – including, some years later, HER2/neu, which in 2012 I learned was a factor in my own breast cancer.

I remember sitting in my surgeon’s office just after my mastectomy, going over my pathology report. We talked about the presence of HER2 overexpression in my tumors. Breast cancer tumors that over express HER2 are often described as more aggressive and faster growing than ones that don’t.

“This used to mean a very poor prognosis, but Herceptin has changed everything,” she said.

The discovery of HER2 led to the development of Herceptin (trastuzumab), a monoclonal antibody that targets the HER2 protein. Now, Herceptin accounts for a 9% increased 10 year survival rate in early stage HER2+ patients. And compared with chemotherapy, Herceptin and other HER2 targeted drugs have much fewer and milder side effects.

Mien-Chie Hung, PhD, a CRI Fellow from 1983 to 1986, was one of the first three to clone the HER2/neu oncogene, a key milestone enabling the development of trastuzumab and other HER2 directed therapies for HER2+ breast cancer. Dr. Hung is currently the vice president for basic research and director of the Breast Cancer Research Program at MD Anderson Cancer Center in Houston, TX.

As a patient who has benefited greatly from this treatment, I’m honored to hold my position here at the Cancer Research Institute. The organization has a long history of funding important, groundbreaking research across all cancer types.

Be sure to tune in to Cancer: The Emperor of All Maladies tonight, for a look at the future of cancer treatment with immunotherapy. If you missed last night’s episode, it is available for streaming.

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