Drug-resistance in skin cancer cells could be combated by alternating chemotherapy with medication-free periods, according to studies on mice.
Anti-cancer drug vemurafenib was hailed as a breakthrough when it came onto the US market in August 2011 (February 2012 in the EU), but evidence since has shown tumours rapidly develop resistance to the drug, often with lethal consequences for patients.
However, a new study, published in the journal Nature, shows that tumours which develop vemurafenib-resistance instead become dependent on the drug to survive. Withdrawing treatment can therefore cause drug-resistant tumours to decrease in size.
Researchers at the University of California, San Francisco, the Novartis Institutes for Biomedical Research in California and University Hospital Zurich in Switzerland carried out experiments on mice with skin cancer, also known as melanoma, to determine why certain cancers become resistant to vemurafenib.
They discovered that the mice’s melanoma cells were altering their internal chemistry to circumvent the effects of vemurafenib, but at the expense of becoming dependent on the drug for survival. The scientists were able to show that ceasing the mice’s treatment, and thus removing the melanoma cells source of vemurafenib, caused tumours to shrink.
The scientists used this discovery to develop a new treatment plan. Instead of a traditional, continuous course of daily medication, the mice were put on a schedule involving four weeks on vemurafenib, then two weeks off, then four weeks on and so on.
Martin McMahon, the UCSF’s Efim Guzik Distinguished Professor of Cancer Biology, said: “Intermittent dosing with vemurafenib prolonged the lives of mice with drug-resistant melanoma tumours.”
Further testing will be required to establish whether these results can be replicated in humans, but, according to Professor Mark Middleton, director of Cancer Research UK’s Experimental Cancer Medicine Centre in Oxford: “These results suggest a way in which this important new treatment might be able to increase the benefit to patients and their families.”
Professor Middleton also said the new method could be a “more cost effective treatment, with fewer side effects.”
Prof Richard Marais, of the Paterson Institute for Cancer Research in Manchester, said: “This new study is exciting because it suggests a way to combat the evolution of drug resistance in melanoma patients using the drugs we already have, rather than having to develop new ones.”
Prof Marais suggested intermittent treatments might prove effective with other targeted cancer drugs.