Breast Cancer Drug Discovered to Expedite Cancer Cell Growth
HER2 receptor protein is chiefly responsible for telling cells to divide- and when it aggregates or when cells have too many copies of this protein, it tends to cause damage in the form of breast cancer. Cells with too many of these proteins, especially breast cancer cells are found to have up to 1000 times too many – divide uncontrollably. And this causes the cancer to grow.
While there are a few efficient HER2 signal blocking anticancer drugs in the market, the most effective ones are found to be those that work by preventing these receptor proteins from building its faulty signals. These are the kinase inhibitors and the most popular of them is called the lapatinib- which was found to be not as successful in clinical trials as the medical community had hoped.
Furthermore, researchers at the Francis Crick Institute have now found this drug to be counterintuitively boosting the growth of breast cancer cells.
“In recent studies, HER2-targeted therapies that combined lapatinib with the antibody treatment trastuzumab successfully controlled HER2-positive breast cancers at first, but did not improve longer-term disease-free survival,” said study co-senior author Tony Ng, MD, PhD, of
Kings College London, according to a press release. “Our new findings could help us design future studies to improve combined HER-targeted therapies.”“If certain breast cancer drugs can cause cancer cells to grow more rapidly in particular circumstances in the lab, we need to evaluate carefully if that might happen in subsets of patients as well,” cautioned the Francis Crick Institute’s Jeroen Claus, Ph.D. “Determining these risk factors could help doctors decide which patients may benefit most from these drugs.”
Lapatinib is used in combination with other cancer drugs and chemotherapy to aid in the treatment of patients with a particular type of advanced breast cancer, but failed clinical trials as a stand-alone treatment.
In the current investigation under discussion, the research team employed a combination of biochemical, biophysical, and computer modelling tools, to discover that this sketchy drug caused HER2 receptors on cell membranes to pair up with a partner receptor called HER3.
They noted that when these inhibitor-induced HER2-HER3 pairs were combined with naturally-occurring growth signals from outside of the cell, they were able to rearrange themselves into an active, signalling pair.
And in this state, it was observed that the HER2-HER3 pair became very efficient at telling the cells to divide, more so than cells that haven’t been treated with the drug.
Peter Parker, joint senior author of the paper and Group Leader at the Francis Crick Institute and King’s College London (KCL) said: “Although our study was in breast cancer cells, it gives us new insights into the nuts and bolts of what happens to HER2 when you try to block it and raises some interesting questions around how we should approach designing drugs against HER2 positive breast cancer in the future.”
Tony Ng, a clinician scientist heading the School of Cancer and Pharmaceutical Sciences at KCL, and joint senior author of the paper said: “In recent patient studies, HER2 targeted therapies that combined lapatinib with the antibody treatment trastuzumab successfully controlled HER2 positive breast cancers at first, but did not improve longer term disease-free survival. Our new findings could help us design future studies to improve combined HER2 targeted therapies.”
Justine Alford from Cancer Research UK, said: “By revealing surprising insight into the biology of HER2 and how this molecule may respond to certain drugs, this important lab research could guide future work into sophisticated new treatments that target HER2 in a more effective way.
“As many breast cancers are triggered by HER2, drugs blocking its action have become cornerstone treatments for these diseases and they’ve shown great success. But sometimes these treatments can stop working, so there is a pressing need to develop new drugs that can overcome this issue and help improve the outlook for these women.”
