Estrogen receptor (ER)-positive breast cancer is the most common form of the disease accounting for about 70 percent of all breast cancers. These tumors require the hormone estrogen to grow. Anti-estrogen therapies – tamoxifen, aromatase inhibitors and fulvestrant – are very effective at treating this type of breast cancer.
Some of these tumors, however, will become resistant to these therapies. In other cases, the cancer returns many years later, often at a different site (a process called metastasis) and these recurrent tumors may already be resistant to anti-estrogen drugs.
BCRF researchers investigate ER resistance
BCRF research couple Drs. John and Benita Katzenellenbogen spoke with BCRF at the AACR Annual Meeting about the work they are doing to reduce drug resistance and improve the patient outcomes.
Of note, Dr. John Katzenellenbogen was the recipient of the 2018 AACR Award for Outstanding Achievement in Chemistry in Cancer Research in recognition of his contributions in cancer research and patient care.
The Katzenellenbogens met while attending Harvard University and have been collaborators ever since. John Katzenellenbogen, a chemist, and Benita Katzenellenbogen, a medical biologist, combine their expertise to study how the estrogen receptor works.
“Combining chemistry with biology is a catalytic force in discovery,” John Katzenellenbogen told BCRF.
Their work led to the identification of mutations in the ER gene that occur in response to AI therapy and cause the tumors to become resistant to the therapy.
On the horizon
In addition, they identified other factors that result in endocrine resistance. One of these is a protein call FOXM1 that regulates genes involved in growth and metastasis. Interestingly, FOXM1 becomes activated in other drug-resistant tumors, such as triple negative and HER2-positive breast cancers, making it an exciting target for other aggressive breast cancers.
The researchers are currently developing a class of compounds to target FOXM1 that they believe will be effective at preventing or treating multiple types of drug-resistant breast cancer.
You can watch the full interview with John and Benita Katzenellenbogen below:
Read more about their BCRF research on our Meet the Researchers page.
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