Sham Kakar
University of Louisville, KY·Medicine & Clinical Research
Ovarian cancer is the deadliest gynecologic cancer. About 70% of patients relapse within two years, often after the tumor becomes resistant to platinum chemotherapy.
- Fields
Medicine & Clinical Research
Pharmacology
- Topics
ovarian cancer
platinum resistance
doxorubicin
- Grants
- 1 known grant, through Apr 2028
What they work on
- Determine the safety, tolerability and maximum tolerated dose of withaferin A, given as oral ashwagandha capsules at 2, 4 and 8 g twice daily, combined with standard liposomal doxorubicin (DOXIL) in 18 patients with platinum-resistant recurrent ovarian cancer.
- Monitor heart function in trial participants to evaluate whether adding withaferin A reduces the cardiotoxicity (heart damage) associated with doxorubicin treatment.
- Use Phase I findings, building on preclinical evidence of synergy and reduced muscle and heart wasting (cachexia), to design a subsequent Phase II trial of the combination.
More about the research
Doxorubicin is an option for second-line treatment, but it can damage the heart. Even its gentler liposomal form, DOXIL (doxorubicin packaged in fat bubbles), helps fewer than 20% of patients with platinum-resistant disease. Better and safer options are needed for these women.
Why it matters
Women whose ovarian cancer returns after platinum chemotherapy have few effective treatments, and doxorubicin's heart toxicity limits its use. Combining liposomal doxorubicin with ashwagandha-derived withaferin A could make this treatment work better and protect the heart and muscles from damage. The Phase I safety data are a needed step toward larger trials in these patients.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Larisa Litovchick
Virginia Commonwealth University, VA·Pharmacology
Test whether high levels of chondroitin-4-sulfate (C4S), a sulfated sugar chain on tumor cells, contribute to platinum resistance in ovarian cancer, using mouse tumor models.
Kandy Velazquez
University of South Carolina-Columbia, SC·Physiology
Determine how TGFβ2, a signaling protein, starts fibrosis (scar-like tissue buildup) and activates M2 macrophages in the skeletal muscle of cancer cachectic mice.
Zahid Siddik
University of Texas MD Anderson Cancer Center, TX·Pharmacology
Test whether reducing MDM4, a natural inhibitor of the p53 tumor suppressor, restores basal p53 phosphorylation in cisplatin-resistant rare ovarian cancer subtype models, both in cultured cells and in animals.
The school
University of Louisville: 15 labs on PI Pages, $225M a year on research, 159 research doctorates a year.
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