The treatment was discovered by a team at USC and has been tested on mice tumors and on ovarian cancer cells. The finding was published in the Proceedings of the National Academy of Sciences (PNAS).
"We need a new generation of drugs," revealed Shili Xu, a USC graduate student and leading author. "We need to overcome the drug-resistance issue."
After analyzing nearly 10,000 chemical compounds on cancer cells, the new drug, a member of a recently developed kind of cytotoxic agents abbreviated as PACMA, was developed in the lab of Nouri Neamati, professor of pharmacology and pharmaceutical sciences at the USC School of Pharmacy.
After the discovery, Nicos Petasis, co-author and professor of chemistry at the USC Dornsife College of Letters, Arts and Sciences, joined the team. The scientists then examined PACMA compounds, publishing the results in the Journal of Medicinal Chemistry.
Alexey Butkevich, a graduate student in the Petasis lab and co-author, synthesized over 80 newly created compounds, in order to explore anticancer properties of PACMAs, while finding the most effective way they can be used.
PACMA31, was one that was found to be extremely deadly to ovarian cancer cells and was demonstrated to be a potentially beneficial drug.
Xu and his team explained that PACMA31 is a powerful and selective inhibitor of a protein called Protein Disulfide Isomerase (PDI) that is highly expressed in this disease.
PACMA31 has a reduced chance of causing dangerous side effects in normal tissues because it accumulates in cancer cells.
The drug is "irreversible", indicating that it will not stop latching on to its target, PDI, and will not wear off until the protein is degraded.
The individuals might be able to take drugs in lower doses if that irreversibility causes drug action to last longer.
"We are exploring combination studies in order to find synergy between our drug and first-line therapy for ovarian cancer," Neamati explained.
At the present time, there are two major classes of drugs in the first-line treatment of ovarian cancer:
- paclitaxel- inhibits cancer cell division by preventing the disassembly of microtubules
- carboplatin- binds to and causes crosslinking of DNA, which causes cancer cells to die
Since this strategy is so unique, it may help those who receive no benefits from paclitaxel or cisplatin.
"When the patient has no other choice, we could potentially treat them with our drug," said Neamati.
"The discovery of this new drug and its novel mechanism of action is a great example of the power of interdisciplinary collaborations between chemists, biologists, pharmacologists and other biomedical researchers," Petasis added.
Further testing needs to be done on this treatment, but as of now it seems to be safe, while successfully stopping tumors from growing, Neamati pointed out.
"Obviously, we think that it will go beyond ovarian cancer," he said.
Written by Sarah Glynn