Combination targets: some drugs may work best when they wor...( SAN FRANCISCO While some targeted ...),Health

SAN FRANCISCO While some targeted therapies drugs developed to attack specific molecules in the critical chemical pathways occurring within cancer cells work well by themselves, increasingly researchers are finding that they work better when teamed with other targeted and conventional therapies.

Reported today at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, multiple-target applications of new and existing drugs are offering new hope in the fight against cancer and drug resistance, from lung and breast cancer to rare tumors of the bile duct.

Synergistic effects of multi-level targeting of the MAPK and PI3-kinase pathways in breast cancer cells: Abstract B 128.

The chemical signaling pathways that control the life cycle of cells offer many important targets for cancer researchers hoping to stop the growth of tumors, yet the complex nature of these pathways may make it impossible to kill a cell with a single therapeutic bullet, as researchers from the University of California, San Francisco, (UCSF) have discovered in a study of breast cancer cells. Their findings suggest that molecules used to inhibit the MEK protein, similar to those being studied to control breast cancer growth, can switch on another pathway that keeps cancer cells from dying.

Their solution is to look elsewhere to see where these pathways intersect, which has allowed them to uncover two targets that, when chemically inhibited at the same time, caused apoptosis cell suicide. This combination therapy approach might make it difficult for cancer cells to resist the disruption of a single protein along a particular signaling pathway.

The chemical networks involved in cell cycle control have a tendencyto be much more complicated than we initially expect, with intersecting pathways and feedback loops, said Michael Korn, M.D., an associate professor in residence at the UCSFs Comprehensive Cancer Ce
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