We study the mechanisms that determine resistance to treatment and relapse in B cell malignancies (especially CLL and DLBCL) and the molecular pathways involved in age-related diseases, with particular emphasis on the role of senescent cells in cancer and ageing phenotypes. We also investigate prognostic/diagnostic markers of ageing and anti-senescent therapies for healthy ageing and as adjuvant treatments for leukemia.
B-cell leukemias are a group of frequent cancers that affect a large number of individuals around the world. Many patients with these diseases cannot be cured with current treatments and so it is important to investigate novel therapies that could improve their quality of life and prognosis. Despite recent advances, many of these cancers initially respond well to treatment, only to relapse soon after and become refractory to drugs. The mechanisms involved in this relapse and resistance are not yet clear. Understanding them is the key to a better survival.
Since 2008, we are studying combination therapies for B cell malignancies to reduce resistance to treatment and relapse. We are characterizing the mutations that confer resistance to leukemia cells and looking for markers that could allow the stratification of patients (i.e. finding the right treatment for each patient, in what is called personalized or precision medicine). Among the factors that contribute to resistance and relapse are senescent cells.
Cellular senescence is a permanent cell cycle arrest in which cells remain metabolically active and adopt characteristic morphologic and genetic changes. Senescence plays a key role in development as well as tumor suppression, since oncogene-induced senescence needs to be overcome in order for cells to be transformed. Despite these important physiological functions, senescence also has a negative impact on the organism. The increase of senescent cells with time is known to contribute to the functional impairment of different organs typically seen in ageing.
Because of this, we and others are developing anti-senescent strategies (collectively known as senotherapies) that could be used as adjuvant treatments in leukemia and other cancers, thus reducing the possibilities of a relapse.
We hope that our studies into the mechanisms of leukemia resistance to treatment and relapse will allow us to (i) define stratification markers that determine which patients could benefit from particular treatments; (ii) characterize novel adjuvant treatments based on anti-senescent drugs that reduce the chances of resistance and relapse; (iii) better understand the mechanisms that determine age-related diseases such as cancer; and (iv) propose strategies to enhance healthy ageing.