Targeting resistance to first-line cancer therapies

While the efficacy of cancer therapies and the spectrum of available treatments has seen important advances in recent decades, even the newest medicines face an old problem: treatments are insufficient to kill all cancer cells.

This can be due to various reasons such as the accumulation of senescence or drug-tolerant persister states, or by the existence of drug-resistance mechanisms.

Regardless of the reason, the incapacity to eradicate all tumor cells is the cause for the emergence secondary tumors, which often present a significantly worse prognosis.

In this context, efforts must be placed to maximize the efficacy of initial treatments, thereby limiting tumor relapse and thus significantly improving the prognosis of the disease.

One of such approaches is known as the “one-two-punch” strategy, which aims to selectively target cancer cells that have endured an initial therapy by a subsequent treatment with another drug.

During the recent years, our laboratory has dedicated significant efforts to understand the mechanisms of drug resistance and how to overcome them.

Moreover, we have established chemical screening pipelines that allow us to discover efficacious drug combinations for cancer therapy.

Building on this line of work, we here propose a comprehensive approach around the “one-two-punch” strategy, where our aim is to discover efficacious drug combinations that can maximize the efficacy of the first-line treatments that are currently being given to cancer patients.