Breast cancer might have a new weakness.
A new method of treating breast cancer can kill 95% to 100% of cancer cells in mice-based analogs, along with their metastases in the brain, lungs, liver, and bones, according to a new study published in the journal Science Translational Medicine.
And the new drug, called ErSO, rapidly shrinks even large tumors to undetectable sizes.
Breast cancer cells protect themselves from damage
The study went forward under the purview of scientists from the University of Illinois Urbana-Champaign. "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 Biochemistry Professor David Shapiro, lead author of the study at the University, along with Chemistry Professor Paul Hergenrother, in an embargoed release shared with IE. "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."
The behavior of ErSO is contingent on that of an estrogen receptor protein that's present in the majority of breast tumors. Once it binds to the estrogen receptor, ErSO clears the way for cancer cells to enter a rapid growth phase, while also protecting them from excess stress. This pathway is called the anticipatory Unfolded Protein Response (a-UPR), which hastens the production of proteins that shield the cell from damage. "The a-UPR is already on, but running at a low level, in many breast cancer cells," explained Shapiro. "It turns out that this pathway shields cancer cells from being killed off by anti-cancer drugs."
The new drug will enter human trials soon
The a-UPR pathway was initially discovered in 2014 by Shapiro and Neal Andruska, a former U. of I. medical scholar. At the time, the pair reported their development of a compound capable of pushing the a-UPR pathway into overdrive, which can kill breast cancer cells that contain estrogen receptors. "Because this pathway is already on in cancer cells, it's easy for us to overactivate it, to switch the breast cancer cells into lethal mode," said Darjan Duraki, another first author of the study, who is also a graduate student. "Since about 75% of breast cancers are estrogen-receptor positive, ErSO has potential against the most common form of breast cancer," said another graduate student involved in the study named Matthew Boudreau. "The amount of estrogen receptor needed for ErSO to target a breast cancer is very low, so ErSO may also work against some breast cancers not traditionally considered to be ER-positive."
Notably, additional exposure of mice to the drug showed no adverse effects on their reproductive systems, and the compound also performed well in rats, dogs, and mice at much higher doses than required for effective therapy. This is marks substantial progress in the fight to eliminate breast cancer with high efficiency and minimal side effects. "Many of these breast cancers shrink by more than 99% in just three days," said Shapiro. "ErSO is fast-acting and its effects on breast cancers in mice are large and dramatic." Human clinical trials will go forward with a Bayer AG license of the new drug, with an eye toward testing ErSO's effectiveness against a broader spectrum of cancers that carry estrogen receptors.