Research Overview
Aging is the most robust risk factor for cancer development, with more than 60% of cancer incidence occurring in those aged 65 and above. Aging not only predicts cancer incidence, but also plays a central role in prognosis. Older patients have worse outcomes with unfavorable progression-free and overall survival rates. This relationship has become even more concerning considering the dramatic increase in the average life expectancy over the last decades. Cancer is currently one of the leading causes of death in the western world, yet the cancer-associated morbidity and mortality rates are predicted to increase as the population continues to age. Despite this, how the aging and tumorigenic processes are intertwined is still not well defined and a matter of debate.
Knudson’s hypothesis that cancer occurs more frequently as one ages because of increased exposure time to mutagens—allowing one’s cells to accumulate sufficient genetic mutations to cause cancer—has been challenged by observations that changes in diet and physical activity can dramatically affect age-induced cancer susceptibility and outcome. On the other hand, the multi-stage model of carcinogenesis (MMC) described by Armitage and Doll and further developed by Nowell, which postulates carcinogenesis as a Darwinian somatic selection process encompassing both cell autonomous (mutations) and non-autonomous (selection) components as driving forces of carcinogenesis, is more in line with the current view of the aging process. Highlighting the role of aging in the tumorigenic paradigm, a recent study suggests that for MMC to be able to describe cancer incidence across tissues and species, it needs to embrace aging-dependent somatic selection. This emphasizes the importance of the systemic and local environments as key contributors to the genetic hits and the tumorigenic process, and suggests that the aging process itself functions both as a driver and a selective pressure that shapes cancer cell fate decisions and conditions patient outcome. Therefore, research in the Gomes Lab is centered in the premise that tumors developing in old hosts are molecularly different entities than tumors found in young hosts, with higher propensity to progress, metastasize and be refractory to conventional therapies.
Our current research is centered on the following topics (click on each for more information):