NCI cancer bulletin

[Maggie]

NCI cancer bulletin for April 11th. This came today!



Study Points to Potential Method for Overcoming Trastuzumab Resistance The inability of some women with HER2-positive breast cancer to clinically respond to treatment with trastuzumab (Herceptin) may be overcome by combining the drug with an agent that inhibits PI3K, an intracellular growth-promoting protein. Researchers from the University of Texas M.D. Anderson Cancer Center, led by Dr. Dihua Yu, a professor in the Department of Surgical Oncology, reported lasted week at the AACR annual meeting that they tested seven different PI3K inhibitors and found that two of them, when combined with trastuzumab, increased its antitumor activity in a breast cancer mouse model.

The study builds on previously published work by Dr. Yu and colleagues, in which women who failed to respond to trastuzumab had tumors with low levels of PTEN, a known tumor-suppressor gene.

Because PTEN exerts its tumor-suppressor function in part by inhibiting PI3K, the group decided to test some PI3K inhibitors in clinical development to see if they could mimic the effect that PTEN would have if it were being expressed at adequate levels. Two of these agents showed antitumor activity when combined with trastuzumab, triciribine, and RAD001 (everolimus). The latter combination, Dr. Yu said, had an additive therapeutic effect on tumor growth in a mouse model of breast cancer compared with trastuzumab alone.

"We think the combination of Herceptin and a PI3K inhibitor is affecting multiple cancer pathways," Dr. Yu said. "It will be interesting to see if other PI3K inhibiting agents now being developed also will work in HER2-positive, PTEN-negative tumors, as well as in other breast tumors that lack PTEN." M.D. Anderson is launching a phase I/II trial to test the combination of RAD001 and trastuzumab in women with HER2-positive breast cancer who have failed to respond to trastuzumab alone as a first-line

Maggie