Despite incredible advances, some cancers remain incurable. Whether it be onslaught by radiation, cell destruction via chemotherapy, or targeted drug therapies to halt tumor growth, some cancers are simply resistant to all weapons scientists use against them. One such cancer is metastatic estrogen receptor-positive breast cancer. This aggressive form of breast cancer is the most common form of breast cancer, yet some cases are entirely incurable due to various mutations that can make it resistant to treatment. However, scientists may have discovered a new weakness – and it’s a big one. In a recent study published in Science Translational Medicine, researchers from the University of Illinois Urbana-Champaign outline a new compound that directly targets human metastatic breast cancer cells and all their metastases (secondary growths around the body as a result of the cancer spreading) in mice, resulting in almost complete tumor regression. They hope the new compound opens a new line of inquiry into halting and destroying the aggressive form of cancer, potentially developing a new class of anti-cancer drugs that could finally combat metastasis. Metastatic estrogen receptor-positive (ERα) breast cancer is special in that it utilizes estrogen as a means to grow. As such, current therapies aim at depleting estrogen in the bodies of afflicted people – stop the "food" source and the cancer cannot grow out of control. Unfortunately, ERα cancers have a tendency to gain mutations that allow them to bypass this limitation and continue to grow, making it much harder to treat and incredibly deadly. To combat this, the scientists have taken an alternative approach and created a new compound called ErSO. ErSO is a small molecule that does not compete with estrogen, like other available drugs, and instead over-activates a pathway in ERα cancer cells to initiate cell death (called the unfolded protein response). When injected into mice, ErSO resulted in complete regression of the breast cancer, including cells that were known to carry mutations making them resistant to other treatments. Furthermore, within 7 days of injection, metastases in the lung, bone, and liver were eradicated, suggesting the compound is not only good at destroying large tumors but also almost entirely removing the cancer from the body. “Even when a few breast cancer cells do survive, enabling tumors to regrow over several months, the tumors that regrow remain completely sensitive to retreatment with ErSO,” said University of Illinois biochemistry professor David Shapiro, lead author alongside Illinois chemistry professor Paul Hergenrother, in a statement. “It is striking that ErSO caused the rapid destruction of most lung, bone and liver metastases and dramatic shrinkage of brain metastases, since tumors that have spread to other sites in the body are responsible for most breast cancer deaths.” In their tests, ErSO had no detectable side effects in the mice. With such promising results, the researchers are moving quickly to understand the scope of ErSO. Pharmaceutical company Bayer AG has already licensed the drug and will explore it further in possible human trials, while the researchers will continue to use ErSO on other estrogen receptor-positive cancers to test how effective it can be. Source
