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Two-Drug Combination Targets Resistance in Cancer

By: Kayci Reyer
Posted: Wednesday, August 14, 2019

According to research published in Oncogene, a combination treatment of the CDK4/6 inhibitor palbociclib and the MET inhibitor crizotinib may prove to be more effective against the replication of cancer cells than either medication as monotherapy. “Our evidence shows that existing medicines could be used to overcome resistance to treatment in a frequent form of breast cancer in women,” noted Sibylle Mittnacht, PhD, of the University College London Cancer Institute, in a press release by The Institute of Cancer Research.

The study involved cancer cells in a laboratory or rodent host setting and included cells from lung, breast, and bowel tissue. Palbociclib often becomes less effective when cancer cells activate the backup molecule CDK2, which also promotes cell division and disease progression. The activation of CDK2 relies on signaling that occurs through a cellular control pathway, a process that relies on two other molecules, MET and FAK.

When crizotinib was combined with palbociclib, the activation of CDK2 was prevented, blocking the division of cancer cells. In addition, the combination also induced senescence, where cell death did not occur but there was a prolonged inactivity in cell growth and division. The two-pronged treatment was found to be more effective in preventing the replication or disease progression of cancer cells in a laboratory or rodent host setting than either medication alone.

“We have shown the potential of combining two precision medicines for breast and lung cancer together to create a two-pronged attack that strips cancer cells of their resistance. We still need to do more work to understand the full potential of combination treatment to increase the effectiveness of these drugs, but the approach looks highly promising and has the potential to be effective against several cancer types,” noted Paul Workman, PhD, of the University College London Cancer Institute, in a press release from The Institute of Cancer Research.

Disclosure: The study authors’ disclosure information may be found at nature.com.



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