Scientists from the Institute of Cancer Research (ICR) in London, UK, have partnered with pharmaceutical firm Cyclacel to synthesise a prototype drug, CCT068127, to simultaneously target both CDK2 and CDK9 proteins commonly found in cancer cells.
A study conducted by the ICR revealed that colon cancer can be treated by combining drugs able to block cancer growth and survival with those that can trigger cancer death.
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During the research, the scientists combined CCT068127 with BCL2-inhibiting drugs, which could stimulate programmed cell death in tumour cells, and found that the combination could aid in the killing of colon cancer cells.
ICR Molecular Drug Resistance team leader Dr Steven Whittaker said: “Our study describes the activity of a potent CDK2/9 inhibitor, which blocks cancer’s growth by hitting two targets at once.
“This is also the first study to show that we could use CDK-inhibiting drugs with other drugs that trigger cell death as an effective combination in colon cancer models.”
ICR researchers developed CCT068127 from an early generation CDK-inhibiting drug called seliciclib. They further optimised the new compound into an experimental drug, CYC065, discovered in alliance with Cyclacel.
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By GlobalDataICR further partnered with the University of Newcastle to use X-ray crystallography for observing the mechanism of CCT068127 after attachment to a specific CDK2 domain.
The study showed that CCT068127 inhibited cancer proliferation through suppression of CDKs and decreased the levels of a protein called MCL1, which was known to protect cancer cells from death.
When combined with an experimental BCL2-blocking drug, CCT068127 was found to have worked more effectively, when compared to alone.
Whittaker added: “We found that our combination tips cancer cells away from signals that promote survival towards death, so it could lead to new ways to treat the disease.”
