麻豆传媒映画

A treatment for the most common type of breast cancer may already exist. As reported in a December paper in , 麻豆传媒映画 researchers who were part of an international study believe they found one.

Associate professor of biology Svasti Haricharan initially approached her early research wondering, 鈥淲hy do some people get cancer and other people don't? Something about it feels so unfair.鈥� As her career progressed she realized there was another way to look at it.

鈥淭he right question is, 鈥榃hy is it that all of us don't get cancer?鈥欌��

Our cells mutate all the time: fortunately, everyone has specialized proteins that constantly scan DNA, targeting and killing mutated cells to ensure they don鈥檛 become cancerous. But some people who do develop cancer are missing a specific DNA repair protein called MLH1, which causes them to become resistant to standard therapies.

To understand why, Haricharan鈥檚 lab honed in on the most common type of breast cancer: estrogen receptor positive (ER+) breast cancer, which makes up 80% of breast cancer cases worldwide and is the most common cause of breast cancer-related death. 

Her group found that in some patients, MLH1 is not missing, but located in the wrong part of the cell, which leads to even more robust resistance to treatment.

鈥淚t should be in the nucleus, where the DNA is, but we were seeing it in the cytoplasm, where there is no DNA,鈥� Haricharan said. 

With 30% of all breast cancer patients resistant to standard therapies and limited knowledge on why and which, if any, of the few available alternative treatments will work, most of these patients do not have positive outcomes.

Currently, ER+ breast cancer patients are treated with standard endocrine therapies that boost MLH1 levels in the nucleus and kill the damaged, cancerous cells. However, many become resistant to this treatment so after three to five years, during which the tumor has grown and spread to other parts of the body, they are given a targeted therapeutic called CDK4/6 inhibitors as a last resort.

In other cases, patients appear to respond well to treatment for years. However, a group of sleeper cells subtly remain, learning how to combat standard treatments, and up to 20 years later, patients relapse with a tumor that is more aggressive and resistant to standard therapies. At that point, even CDK4/6 inhibitors can be ineffective. Physicians are unable to predict which patients carry these sleeper cells. 

But Haricharan鈥檚 lab made a finding that points toward a new treatment, pending additional tests.

Their study showed that, for ER+ breast cancer cells where MLH1 is located in the wrong place, an early intervention with CDK4/6 inhibitors in most cases doesn鈥檛 just prevent tumors from growing, but shrinks them.

鈥淲e found that when we have this cytoplasmic mislocalization protein, although patients are resistant to standard therapies, they are sensitive to CDK4/6 inhibitors, which is safe, available and FDA approved for certain types of breast cancer,鈥� Haricharan said. 鈥淭his is a new indication for patients who can be eligible for that therapy, and would likely respond better to that than the standard therapy alone.鈥�

Haricharan鈥檚 team is now organizing a clinical trial to further test this theory which they think can boost survival rates.

鈥淭he reason we are excited about it is that the diagnostic already exists and is clinically certified, and the therapeutic already exists and is FDA approved,鈥� she said. 鈥淭his is just repurposing an existing drug to a new patient population, which means it can be given to patients right now, so to speak.鈥�

Haricharan鈥檚 study also seems to suggest the sleeper population could be the cells with MLH1 in the cytoplasm instead of the nucleus.

鈥淓ven a very small subset of cells can likely induce resistance years down the line,鈥� she said. 鈥淭hat is why we think it is really important to give the intervention early on, so you don't let the sleeper population evolve and become more dangerous, but try to kill it early on so your resistance probability is significantly decreased.鈥�

In addition to 麻豆传媒映画, the 18 listed authors of the study included researchers from UCSD Moores Cancer Center, Sanford Burnham Prebys Medical Discovery Institute (La Jolla), Temple University, European Institute of Oncology IRCCS (Milan, Italy), University of Milan, and Rady Children鈥檚 Institute for Genomic Medicine, San Diego.

This work was funded by the National Cancer Institute, the U.S. Department of Defense Breast Cancer Research Program and the American Cancer Society.