Targeted Attack

Molecular Rationale for Combining Agents Against Breast Cancer

Tim HM HuangA study by researchers at the OSUCCC – James presents a rationale for treating breast cancer using two targeted agents: one that inhibits an overactive, cancer-causing pathway in cancer cells, and one that reactivates silenced tumor suppressor genes. Both types of agents are currently being evaluated individually in clinical trials.

The laboratory and animal study found that abnormal activation of the PI3K/AKT signaling pathway leads to the silencing of a number of tumor-suppressor genes that regulate cell proliferation, survival and motility, and angiogenesis. The study also showed that tumor growth is slowed by combining an agent that inhibits PI3K with a drug that reverses the epigenetic changes that cause gene silencing.

Targeted Attack-2“The link we have uncovered between PI3K/AKT signaling and epigenetic silencing offers a new therapeutic strategy for breast cancer that combines a PI3K/AKT inhibitor and agents that target epigenetic changes,” says study leader Tim H-M Huang, PhD, of the OSUCCC – James’ Molecular Biology and Cancer Genetics Program.

The activation of one or more oncogenes and the silencing of tumor-suppressor genes are usually considered separate events that together lead to cancer. But this and earlier studies led by Huang show that the two events are sometimes linked.

Huang and colleagues are planning a clinical trial that will investigate the use of combined targeted drugs in metastatic breast cancer.

Published in the journal Cancer Research.

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