New Generation of Ovarian Cancer Drugs?

Ovarian cancer may have new treatment in PACMA31

(RxWiki News) Ovarian cancer tends to respond to treatment initially. Then the disease becomes resistant to the drugs being used and returns. A new type of drug currently being studied may change this lethal trend.

A drug currently being studied in early laboratory and animal studies may offer better treatment options for women with ovarian cancer. The drug is part of a class of drug chemotherapy agents known as PACMA.

"Find out the track record of the chemotherapy you’re receiving."

Researchers at the University of Southern California are conducting this study which could lead to a new drug that requires fewer doses to work and may also overcome the resistance problem.

"We need a new generation of drugs," said Shili Xu, a USC graduate student and lead author of the paper. "We need to overcome the drug-resistance issue."

The drug, which has been tested in ovarian cancer cells and in mice tumors, is part of a class of drugs abbreviated as PACMA - propynoic acid carbamoyl methyl amides.

PACMA was found after testing some 10,000 chemical compounds on cancer cells. This was the discovery of Nouri Neamati, PhD, professor of pharmacology and pharmaceutical sciences at the USC School of Pharmacy, and one of the authors of this paper.

Dr. Neamati collaborated with Nicos Petasis, PhD, another paper author and professor of chemistry at USC.

Researchers synthesized more than 80 new compounds. One of them – PACMA31 – was effective against ovarian cancer cells and could turn out to be a new therapy for the disease that’s diagnosed in just over 22,000 women in the US every year.

PACMA31 works by zeroing in on a protein that’s seen in high levels of ovarian cancer - protein disulfide isomerase (PDI).

The compound can be taken in pill form and it accumulates in cancer cells, while leaving normal tissues untouched.

PACMA31 is also what’s called an irreversible drug, meaning it latches onto its target – in this case PDI – and doesn’t let go until the protein has been degraded.

This feature could mean that lower doses of the drug may be needed.

"We are exploring combination studies in order to find synergy between our drug and first-line therapy for ovarian cancer," Dr. Neamati said in a press release.

Standard therapies for ovarian cancer include paclitaxel (sold under the brand name Taxol and Abraxane) and carboplatin, both of which work by targeting different molecules. PACMA31 attacks cancer cells in yet another way.

The different mechanisms of PACMA31 may help women who become resistant to currently available chemotherapies.

"When the patient has no other choice, we could potentially treat them with our drug," Dr. Neamati said.

The drug needs additional study and is likely years away from being available to patients. At this point, though, it appears to be effective, without toxic side effects, according to the researchers.

Dr. Neamati thinks PACMA31 may have uses that extend beyond ovarian cancer.

This paper was published in September in the Proceedings of the National Academy of Sciences (PNAS).

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Review Date: 
October 9, 2012