Combining targeted drugs for breast and lung cancer could be used in patients with other tumour types to help them overcome treatment resistance, British researchers report today.
Pairing the breast cancer drug palbociclib with the lung cancer drug crizotinib was significantly more effective against cancer cells in the laboratory than either drug used on its own.
The new findings, published in Oncogene, also suggest combining could widen the clinical use of palbociclib, and other drugs that work in the same way, beyond breast cancer to other tumour types.
Scientists at The Institute of Cancer Research, London, and UCL Cancer Institute discovered that resistance to palbociclib, a drug for hormone receptor-positive breast cancer, used is often driven by a protein which is targeted by crizotinib.
Palbociclib is blocks the function of CDK4 and CDK6, which promote tumour cell division and cancer progression. However, cancers can become resistant to palbociclib by activating CDK2.
In this study, the research team discovered 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.
They then found that pairing CDK4/6 inhibitors such as palbociclib with crizotinib – was more effective than either drug on its own against cancer cells grown in the lab or human tumours growing in mice.
The researchers hope that their discoveries can be translated to patients.
Study co-leader Professor Paul Workman, chief executive of The Institute of Cancer Research, London, said: “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.”
Study co-lead Professor Sibylle Mittnacht, Professor of Molecular Cancer Biology at UCL Cancer Institute, added: “Our evidence shows that existing medicines could be used to overcome resistance to treatment in a frequent form of breast cancer in women.
“In addition, use of a current breast cancer medicine together with these other medicines could be a new, promising route for the treatment of lung and several other cancers.”
Oncogene 12 July 2019
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