October 4, 2012
New Drug Option Developed for Ovarian Cancer
Connie K. Ho for redOrbit.com — Your Universe Online
A new study from scientists at the University of Southern California shows that a new drug could be used to help ovarian cancer patients who have not been receptive to drugs that are currently available and possibly reduce the drug dosage needed to be taken.In particular, the drug has been tested in a lab with ovarian cancer cells and on mice tumors. It is part of a group of cytotoxic agents, known as PACMA, that was discovered after experimentation on 10,000 different chemical compounds on cancer cells.
“We need a new generation of drugs," explained the PNAS study´s lead author Shili Xu, a USC graduate student, in a prepared statement. "We need to overcome the drug-resistance issue."
Last year, researchers started a study that looked at the anticancer traits of PACMA by synthesizing over 80 newly created compounds. One of the compounds, PACMA31, was discovered to be toxic to ovarian cancer cells. Subsequently, it was found to be a possible effective drug as it is a selective inhibitor of Protein Disulfide Isomerase (PDI) that has been found in ovarian cancer.
Taken orally, PACMA31 can gather in cancer cells and is less likely to have negative side effects on normal tissues. It is an “irreversible” drug that focuses on PDI and doesn´t stop working until the protein is completely degraded. The researchers believe that the prolonged strength of PACMA in fighting the PDI can translate to a reduction in the dosage of drugs given to cancer patients.
"We are exploring combination studies in order to find synergy between our drug and first-line therapy for ovarian cancer," noted Nouri Neamati, a professor of pharmacology and pharmaceutical sciences at the USC School of Pharmacy who initiated the study on the 10,000 chemical compounds on cancer cells, in the statement.
The researchers believe that PACMA31 targets cancer cells by targeting PDI and prohibiting the folding process of proteins in taking on the shapes needed to function correctly. The drug differs from the two drugs currently used to treat ovarian cancer. While the drug paclitaxel works on preventing cancer cell division by stopping the disassembly of microtubules, the drug cisplatin created crosslinking of DNA to eliminate cancer cells.
With PACMA31, the accumulation of misfolded proteins can lead to cellular stress and cancer cell death. The scientists note that different process of PACMA31 could become an alternative to patients who have not responded to paclitaxel and cisplatin. The study´s results will benefit a percentage of the population that suffers from ovarian cancer. According to the U.S. Centers for Disease Control and Prevention (CDC), in 2008, 21,204 women in the U.S. were diagnosed with ovarian cancer. As well, 14,362 women were reported to die due to ovarian cancer in the same year.
"When the patient has no other choice, we could potentially treat them with our drug," continued Neamati in the statement.
In moving forward, the researchers plan to complete further testing and believe that the drug could be developed to treat other forms of cancer.
"Obviously, we think that it will go beyond ovarian cancer,” concluded Neamati in the statement.
The USC researchers detailed the study´s findings in the Proceedings of the National Academy of Science (PNAS).