Chemotherapy is the tool of choice to slow down the evolution of most cancers. Successful chemotherapy will track and kill all cancer cells while avoiding attacking the healthy cells of one’s organism. Unfortunately this therapeutic ideal is seldom attained because cancer cells naturally have certain means to resist the action of chemotherapeutic agents.

Chemotherapy and resistance

In fact, cancer cells generally react well to a first round of chemotherapy. Their number decreases to a level where their presence cannot be detected anymore and the patient is then considered in remission. This more or less long calm spell unfortunately is still too often followed by a relapse. However, some cancer cells more resistant than average can indeed survive the first offensive of chemotherapy. Being very few, they are not easily detectable up to the moment when, having recovered from chemotherapy insults, they start dividing at a fast pace. Reapplying the initial therapeutic protocol generally turns out to be ineffective on these cells and increasing doses may exacerbate side effects to an unacceptable level. Even opting for a different arsenal of chemotherapeutic agents may not make it possible to break this resistance. The cancer cells have now develop resistance to multiple chemically and functionally unrelated anti-tumor compounds. This phenomenon is called multi-drug resistance.

What is the molecular mechanism underlying this drug resistance?