​The goal of anti-cancer treatments is to specifically remove tumors with no negative impact on healthy cells. Chemotherapy targets a special feature of the cancer cells, which is their rapid proliferation. Yet some cancer cells in the prostate are resistant to treatment, causing relapses. "Unlike other prostate cancer cells, which proliferate very quickly and die in response to chemotherapy, these cells stop growing and behave like differentiated normal cells," said Maxim Balakirev, researcher at CEA-BIG. "As a consequence, these singular cancer cells are not targeted by the treatment. They actually resist it and enter a 'quiescent state'. When the treatment stops, they 'awaken' and begin to proliferate again."

What would make it possible to overcome such resistance and prevent prostate cancer cells from "dozing off"? "Higher doses of chemotherapy would be a way of overcoming it," Balakirev said. "Yet this solution needs to be avoided due to its toxicity." So what is the solution? The researchers showed that suboptimal drug concentration suppresses a molecular pathway called NFκB and activates a program of differentiation, leading to a halt in cell growth and reversible quiescence. This program can be bypassed by targeting the androgen receptors (AR). "We propose a combined therapeutic strategy, which would involve adding a molecule targeting the AR receptors to the antiproliferation treatment to eliminate all cells, including those that resisted," Balakirev said.