Why are some patients resistant to cisplatin chemotherapy for cancer?
In patients who receive cisplatin therapy, their own DNA mismatch protein PMS2 normally plays a key role in helping the drug destroy the cancer cells.
There are a dozen variations of human PMS2, and Drs. Wang and Kolodner have found that cisplatin’s antitumor effects are blocked when one particular PMS2 variant is active.
The findings pave the way for further studies to confirm this discovery and apply it to the challenge of selecting the best chemotherapy regimen for each patient.
Richard Kolodner, Ph.D., is Distinguished Professor of Medicine, Leader of the Cancer Genetics Program at the Moores UC San Diego Cancer Center, and Executive Director for Laboratory Science and Technology at the Ludwig Institute for Cancer Research.
Earlier this year, Dr. Kolodner was honored with election to the American Academy of Arts & Sciences (AAAS).
Drs. Wang and Kolodner are faculty members in the Division of Hematology-Oncology.
Their report was published online September 3, and in print in the September 16 issue of the Proceedings of the National Academy of Sciences:
Marinovic-Terzic I, Yoshioka-Yamashita A, Shimodaira H, Avdievich E, Hunton IC, Kolodner RD, Edelmann W, and Wang JYJ. Apoptotic function of human PMS2 compromised by the nonsynonymous single-nucleotide polymorphic variant R20Q. Proc. Natl. Acad. Sci. USA. 2008; 105:13993-13998. | Read the report (PDF)