Combination of breast and lung cancer drugs ‘may overcome treatment resistance’

Pairing targeted drugs for breast and lung cancer could overcome treatment resistance Credit: David Davies/PA

Combining two drugs for breast and lung cancer could potentially strip other tumours of their treatment resistance, a new study suggests.

Scientists discovered that when breast cancer drug palbociclib was combined with 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.

Scientists at The Institute of Cancer Research, London (ICR), and UCL Cancer Institute discovered resistance to palbociclib is often driven by a protein which is targeted by crizotinib.

But the combined agents acted together to block cancer cell division and induce senescence – a state in which cells are thought to stop growing and dividing but without undergoing cell death.

They were was effective when used against cancer cells grown in the lab on human tumours growing in mice.

And researchers saw promising results in cancer cells derived from different organs in the body – from breast and lung to bowel.

Palbociclib is one of a group of drugs currently used to treat patients with hormone receptor-positive breast cancer by blocking the function of two proteins – CDK4 and CDK6.

However, cancers can become resistant to palbociclib by activating a related molecule called CDK2.

The scientists say their research indicates there is potential to expand clinical use of palbociclib and other CDK4/6 inhibitors beyond breast cancer to benefit a wider range of patients.

Published in the journal Oncogene and funded by Wellcome, the study states it may be possible to develop tests to identify which patients would benefit from the use of crizotinib in this way.

The researchers hope their discoveries can be translated to patients, initially by evaluating the safety and effectiveness of combining the two types of drugs.

Study co-leader Professor Paul Workman, chief executive of the ICR, 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, said: “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.”