Personalização dos programas de exercício físico no cancro da bexiga: o sexo importa?

Strong epidemiological evidence suggests that regular physical activity is linked with a reduced risk of various cancer types, as highlighted in the International Agency for Research on Cancer (IARC) 2021 report. Exercise training (ExT) elicits various biological effects, such as reducing inflammation, enhancing immune surveillance, and modulating hormone and growth factor levels. However, the existing literature predominantly focuses on aerobic exercise (AEx), leaving uncertainties about the impact of resistance exercise (REx) on tumor growth and the microenvironment. Additionally, it remains unclear whether men and women respond similarly to ExT in terms of anticancer effects. Given the differing demands that AEx and REx impose on skeletal muscle (SkM), coupled with sex disparities in SkM mass and distribution, it must be explored whether these differences affect the secretion of bioactive molecules derived from SkM. These molecules may influence inter-organ communication, potentially impacting cancer progression. SEXFIT2CARE aims to address these critical knowledge gaps and advance our understanding of the interplay between exercise and cancer. Therefore, project’s specific goals are: i) To investigate the impact of different ExT programs on bladder cancer (BCa) development and related outcomes. ii) To examine the effect of sex on the interplay between ExT and cancer. iii) To uncover the molecular mechanisms driving the effects of ExT on cancer development and progression, considering sex differences. iv) To define molecular profiles specific to sex and ExT that correlate with health outcomes. v) To identify circulating bioactive molecules, extracellular vesicles and/or extracellular organelles that mediate ExT-sex interplay on cancer development. The accomplishment of these goals will be achieved through the following actions: 1. Implementing a preclinical model of BCa subjected to different training protocols (AEx and REx) that mirror the human scenario. 2. Assessing the impact of sex and ExT programs on bladder carcinogenesis. 3. Characterizing the systemic adaptations associated with ExT-induced outcomes on BCa. 4. Identifying circulating mediators of the effects of ExT programs on male and females using state-of-the art Omics. 5. Evaluating the role of SkM secretory activity in the anticancer effects of ExT programs across different sexes. 6. Project management and dissemination activities. By pursuing these objectives, SEXFIT2CARE will provide robust molecular evidence supporting ExT for cancer management. It also endeavours to support the definition of guidelines for optimizing the health benefits of ExT in cancer settings, considering sex-specific factors. Additionally, it will establish whether a molecular profile can reflect tumor severity and overall health status, with the ultimate goal of validating this in clinical settings to facilitate the monitoring of patient response to ExT. Furthermore, the identification of bioactive molecules responsible for the anticancer effects of ExT may lead to the development of innovative therapeutics derived from ExT effects. This could offer promising options for patients unable to engage in physical activity.