As we continued our studies on cancer development and progression, we encountered therapy-induced senescence (TIS), a cellular fate induced by radiation and chemotherapy in both normal and tumor tissues. TIS is characterized by an irreversible exit from the cell cycle and the secretion of the Senescence-Associated Secretory Phenotype (SASP). The accumulation of senescent cells leads to tissue dysfunction and organ failure, contributing significantly to the side effects observed in cancer patients post-treatment. Additionally, these cells accumulate with age, contributing to frailty and decreased longevity.

Our data indicate that senescent cells rewire their ER-mitochondria communication, making them sensitive to InsP3R inhibition. Our current efforts focus on understanding the dynamics of ER-mitochondrial communication in the initiation and establishment of cellular senescence, with the ultimate goal of selectively targeting these cells or preventing their appearance. We are also investigating the role of other organelles, such as lysosomes, in this inter-organellar communication.

One of our groundbreaking discoveries is the vital importance of ER-mitochondria calcium communication in cancer cells. Disrupting this communication selectively kills cancer cells, offering a promising therapeutic target. This discovery has driven us to delve deeper into the molecular pathways and key players involved, developing molecular and pharmacological tools to manipulate this interaction.

Our research reveals that intracellular calcium communication extends beyond the ER and mitochondria, involving other organelles such as lysosomes and the plasma membrane. This broader understanding opens new avenues for therapeutic interventions.

Interventions such as ketogenic diets, NAD supplementation, and exercise have been reported to improve aging and the quality of life for cancer patients. However, the impact of these interventions on inter-organellar communication and cellular senescence remains unknown. We have launched a series of experiments to explore these effects and are also investigating new methods to modify inter-organellar communication, such as the use of postbiotics.