Hybrid cancer drug could be resistance-resistant

A team of cancer researchers led by scientists at UC San Francisco and Memorial Sloan Kettering Cancer Center demonstrated in human cells and mouse models that a first-of-its-kind hybrid drug can outsmart drug-resistant cancers. The new drug physically yokes together two existing drugs against a common cancer pathway into a single molecule, generating a double-blow that blocked the resistance cancer cells otherwise develop to either drug on its own.

The researchers, who published their finding online on May 18, 2016 in the journal Nature, hope that their new approach will lead to a whole class of new therapies that keep cancer at bay much longer and improve patient survival.

"Every time we find a new drug target against cancer, we go through one, two, three generations of drugs as the cancer keeps evolving resistance," said study co-senior author Kevan Shokat, Ph.D., professor and vice-chair of the department of cellular and molecular pharmacology at UCSF. "What we really wanted to do was get out ahead of this cycle of resistance."

Researchers unravel mechanisms of drug resistance in common cancer pathway

Precision medicine approaches to cancer, which involve targeting the specific mutations driving an individual patient's disease, run the risk of promoting treatment-resistant tumors by killing off drug-sensitive cancer cells and allowing a minority of mutant, drug-resistant cells to thrive in their place.

Mutations driving over-activation of the protein mTOR—a key molecule regulating cellular growth, division, proliferation, and other important functions—are common factors of many different cancers, making mTOR a key target for anti-tumor therapies. The drug rapamycin and similar therapies that interfere with mTOR's function (such as everolimus, or Afinitor, and temsirolimus, also known as Torisel) have been approved for the treatment of a several cancers, including kidney cancer, pancreatic neuroendocrine tumors, and advanced breast cancer.

Unfortunately, tumors treated with these first-generation mTOR inhibitors often evolve resistance to these drugs. Second-generation mTOR inhibitors, which work by jamming mTOR's ATP site – it's molecular "engine"—are currently in clinical trials, but tumors will assuredly evolve resistance to these drugs too in time, researchers say.

Members of Shokat's laboratory, in collaboration with the researchers in the lab of co-senior author Neal Rosen, M.D., Ph.D., the Enid A. Haupt Chair in Medical Oncology at Memorial Sloan Kettering Cancer Center, began to search for new approaches to attacking these cancers that might avoid the trap of resistance.


Read more at: http://phys.org/news/2016-05-hybrid-cancer-drug-resistance-resistant.html#jCp

Good news. Let's hope this works and helps thousands of people.