A new study has shown that targeted drugs for breast and lung cancer could be used together to overcome resistance to treatment in several different tumour types.
Scientists discovered that when the breast cancer drug palbociclib was combined with the lung cancer drug crizotinib, the two-drug combination was significantly more effective against cancer cells in the laboratory than either drug used on its own.
The new data could broaden the clinical use of palbociclib – and other drugs that work in the same way – beyond breast cancer to include many other tumour types as well.
Palbociclib is one of a group of drugs which are currently used to treat patients with hormone receptor-positive breast cancer by blocking the function of two proteins – CDK4 and CDK6 – which promote tumour cell division and cancer progression.
However, cancers can become resistant to palbociclib by activating a related molecule called CDK2, which is able to drive cell division in the absence of CDK4/6.
In the new study, the researchers found that CDK2 can compensate for inhibition of CDK4/6 in cancer cells by signalling via a cellular control pathway involving the key molecules MET and FAK.
Based on this discovery, the researchers found that pairing CDK4/6 inhibitors such as palbociclib together with crizotinib – which blocks MET activity – created a combination treatment that was much more effective than either drug on its own against cancer cells grown in the lab or human tumours growing in mice.
Study co-leader professor Paul Workman, chief executive of The Institute of Cancer Research, explained that ““Cancer’s ability to adapt, evolve and become drug resistant is the biggest challenge we face in creating more effective treatments for the disease. In this study, we sought to understand exactly how resistance occurs to an important family of breast cancer drugs, so that we can stay one step ahead of the cancer.
“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.”
The new study is published in the journal Oncogene and was funded by Wellcome.