Joaquin Arribas, PhD

Developing novel therapies that utilize the power of the immune system to treat breast cancer.

Impact

Normal cells respond to damage by halting cell division, putting the cells in a state of cellular senescence. Similarly, malignant cells will become senescent, a process called senolysis, in response to some therapies. While senescent tumor cells no longer proliferate, they remain molecularly active and produce factors that promote aggressiveness in neighboring tumor cells. Dr. Arribas’ team is focused on developing novel strategies that redirect the immune system against senescent cells, thereby eradicating them and increasing the efficacy of breast cancer therapies.

Progress thus far

Dr. Arribas and his colleagues developed experimental models that helped to establish that cellular senescence can exert either anti- or pro-tumorigenic effects depending on the stage of the tumor and the immune cells present in the immediate tumor environment. Preliminary studies indicate that senescent cells promote the anti-tumor immune response at early stages of tumor formation while inhibiting it at later stages. Dr. Arribas’ group previously identified the factors and mechanisms that mediate the pro-tumorigenic effects and have designed a novel therapeutic strategy to exploit their findings. Specifically, their novel strategy combines therapies that promote senescence with others that mediate the pro-tumorigenic effects. Thus, this combination preserves the anti-tumorigenic effect of senolysis while avoiding its undesired effect of accelerating premalignant lesions.

What’s next

In the coming year, Dr. Arribas and his team will test whether this novel combination therapy has anti-tumor effects on advanced tumors. To accomplish this, they will develop laboratory models that mimic both early and advanced lesions. With validation of their models in place, they will treat each with chemotherapy alone or in combination with a senolytic agent and drugs that prevent tumor progression. By identifying the factors and mechanisms behind the undesired effects of senolysis this research has provided a new avenue to enhance the use of senolytic drugs. and expand the number of anti-tumor tools for treating breast cancer.