US scientists have identified a way in which cancer cells can become resistant to the cancer drug cetuximab (Erbitux), and suggest that treatments that are already available might be able to overcome this resistance. Researchers from the Dana-Farber Cancer Institute in Boston, US, have been studying why some patients only experience short-term benefits with cetuximab, or none at all.
Cetuximab is an antibody that interferes with cancer cell growth. It can be given in combination with chemotherapy to patients with bowel cancer or head and neck cancer. Until now, scientists didn’t know why some cancers failed to respond to the drug, or initially responded but then became resistant.
The new study, published in Science Translational Medicine, found that in some of the drug-resistant cells, a protein known as ErbB2 (also known as HER2/neu) was sending ‘grow’ signals. These were bypassing the ‘stop growing’ signals caused by the drug.
Pasi Janne, the study’s co-senior author, said: “ErbB2 activates a critical signalling pathway that is not normally blocked by cetuximab, and in this way subverts cetuximab’s function.
“Because ErbB2 isn’t affected by cetuximab, this is an easy way for cancers to become resistant to the drug.”
The researchers suggest that combining cetuximab with already available ErbB2 inhibitors such as trastuzumab (Herceptin) could produce an effective therapy to tackle cancers that previously showed resistance to cetuximab.
Henry Scowcroft, science information manager at Cancer Research UK, said: “Unfortunately, patients’s tumours can become resistant to treatment, and understanding why this happens is a major challenge in cancer research.
“This new study is a great example of how researchers are uncovering the molecular tricks cancer cells use to evade treatment, and finding out how to stop them doing so.
“Research like this gives us tremendous optimism that we’re on the cusp of a real revolution in cancer, although there’s a lot more work to do to make this a reality.”
Yonesaka, K. et al. (2011). Activation of ERBB2 Signaling Causes Resistance to the EGFR-Directed Therapeutic Antibody Cetuximab Science Translational Medicine, 3 (99), 99-99 DOI:10.1126/scitranslmed.3002442