Novel Kinase Inhibitors Return Cancer Cells to Normalcy

Cancer researchers have described a novel drug treatment that allows normal cells to communicate with nearby tumor cells and transmit molecular signals that stop the uncontrolled growth of the cancer cells and return them to a normal phenotype.

Investigators from the University of Manchester (UK) prepared 64 novel structural analogues of the kinase inhibitor Y27632. These compounds were tested on mixed cultures of normal cells and cancerous NIH3T3 cells that had been transformed by the constant activation of RhoA-dependent RhoA kinase (ROCK) signaling.

Results published in the August 25, 2009, online edition of the British Journal of Cancer revealed that four of the Y27632 analogues inhibited ROCK signaling. When the NIH3T3/normal cell mixed cultures were treated with these drugs, the NIH3T3 cells stopped growing. The effect of the drug appeared to be permanent, as the cancer cells did not start growing again after the drug was removed. The drugs had little effect on pure NIH3T3 cultures.

"When we added the chemicals to a mixture of healthy and cancerous cells in a flask the diseased cells stopped multiplying and began acting like normal cells again,” explained senior author Dr. Ian Hampson, professor of gynecological oncology at the University of Manchester. "Further tests revealed that the chemicals helped the cancer cells form connections with surrounding healthy cells that allowed these normal cells to take charge of the mechanism by which cancer cells divide and grow out of control.”

Importantly, the drugs did not appear to be toxic to either normal or cancer cells. "When the chemicals were added to a culture containing just cancer cells they had little effect,” said Dr Hampson. "It was only when we added the chemicals to a mixture of cancer cells and normal cells--similar to how you would find them in the body--that growth was suppressed. Intriguingly, the connections that allowed the healthy cells to communicate with the cancer cells stayed open even when the kinase inhibitors were removed indicating that a potential drug based on these chemicals could be given as a short course of treatment. Furthermore, the chemicals are nonpoisonous and do not actually kill cells like conventional cancer therapies, such as chemotherapy and radiotherapy, so if we were able to develop a drug it is likely to have far fewer side-effects.”

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