Combining Breast, Lung Cancer Therapies Could Overcome Treatment Resistance

Combining Ibrance (palbociclib), a treatment for advanced breast cancer, with the lung cancer medicine crizotinib is more effective against human cancer cells in the laboratory than either drug alone, scientists have found.

The researchers say the findings suggest the combination could be used to overcome treatment resistance in some breast cancers, as well as broaden the clinical use of Ibrance as a promising treatment for many other tumor types, including lung cancer.

Their study, “Signalling involving MET and FAK supports cell division independent of the activity of the cell cycle-regulating CDK4/6 kinases,” was published in the journal Oncogene.

“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,” study co-leader Paul Workman, chief executive of The Institute of Cancer Research, London, said in a press release.

According to scientists, Ibrance (by Pfizer) has been one of the more important advances in the past two decades for ithe treatment of women with advanced breast cancer. It is used to treat patients with hormone receptor (HR)-positive, HER-2 negative advanced breast cancer, and works by blocking the function of two proteins — CDK4 and CDK6 — that promote tumor cell growth and cancer progression.

Scientists at The Institute of Cancer Research and London’s UCL Cancer Institute found that cancer cells can become resistant to Ibrance by activating a related molecule called CDK2, which is able to support cell replication in the absence of CDK4/6.

CDK2 is able to do so via a biological pathway involving two other key factors, called MET and FAK.

Knowing this, researchers thought that adding another anti-cancer medicine that blocks MET — crizotinib (sold as Xalkori by Pfizer and EMD Serono) — could be a feasible strategy for improving cancer treatment.

Crizotinib is currently used for the treatment of some patients with metastatic non-small cell lung cancer (NSCLC).

The team could confirm, either in cancer cells growing in the lab or human tumors grown in mice, that combined treatment with Ibrance and crizotinib was much more effective than either agent alone.

Both agents acted together to block cancer cell division, but also to induce senescence — a state in which cells are thought to irreversibly stop dividing and enter a state of permanent growth arrest without dying.

Promising results were noted for different types of cancer cells derived from different organs, including the breast, lung, and colon. Researchers said this indicated the potential to expand clinical use of Ibrance and other CDK4/6 inhibitors to other types of tumors beyond breast 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,” said study co-lead Sibylle Mittnacht, professor of molecular cancer biology at UCL Cancer Institute.