Editorial: Flatten the rising incidence of cancer due to aging

As an oncologist engaged for 45 years in providing ongoing patient care I witnessed a cancer treatment revolution. Multiple options to conventional cytotoxic chemotherapy emerged that led to changing cancer from a rapid fatal disease to a more treatable chronic ailment.  Science was paying off by diminishing the catastrophic effect of cancer for a large number of patients. More people were being cured with less toxic treatments. A significant gain in outcome BUT, my patients were returning with late onset metastases and new primary cancers, this time more difficult to treat and often  associated with the  comorbidities of AGING. This scenario is a global experience. Cancer incidence is increasing in most forms of cancer and mortality rates rising relentlessly with increasing age. The reality is that understanding AGE-related cancer, its evolution, interplay, clinical recognition, and management is underfunded and is an unmet clinical need. As recently as 2015, there has been minimal interactions between the National Cancer Institute and the National Aging Institute to promote research at the interface of aging and cancer, despite the overt links between these processes. Indeed, a major DISPARITY both in research and treating age-related cancer exists.

Yet, ANSWERS are within reach to guide collaborative research to flatten the rising incidence of cancer due to aging. A more holistic view for how aging impacts cancer gaining ground. Aging stem and progenitor cells strive to survive in a changing and often hostile aging stromal environment. This results in somatic variants, epigenetic compensations, loss of gene stability due to DNA damage, and mechanisms to resist exhaustion and death such as reducing immune recognition and hijacking senescence and autophagy  pathways for survival. These changes may be apparent by measurement of clonal progenitor populations with mutations allowing epigenetic driven pathways and cell cycle alterations to emerge to create a survival advantage. Is this privileged and more compensated AGED cell an outlier that is already on a path to cancer clonal evolution and can this be prevented? Clinical and laboratory evidence supports this and  collaborative research is providing models to understand ways to recognize this  transition and identify this threat with precision in the aging cell population. Interventions to diminish age as a risk factor for cancer include education on the importance of “Healthy Aging” and laboratory measurements to distinguish a healthy aged tissue from one with cancerous clonal evolution. Therapeutic interventions to diminish  cancer development in the AGED cell population include early clinical screening, senolytics, specific inhibitors of cell cycle mediators of autophagy, PARP inhibitors, and identifying specific dietary and metabolic dependencies needed to prevent cancer transformation. This type of early screening of AGING stem cells and progenitors and evolving clonal cancer cells and clinical intervention is in its infancy and requires making cancer as a disease of AGING, a major recipient of NIH funding and pharmaceutical investment. This third issue of Aging AND Cancer provides a glimpse of this future and will further the goal of the Samuel Waxman Cancer Research Foundation (SWCRF) to create an international collaborative network on aging and cancer research.