Interested in aging and cancer. I did a year of literature survey on this.
Here is my list of 20 key open questions and challenges to better understand the interplay between aging and cancer. A thread 🧵👇
The presence of mutated clones in aging but otherwise healthy tissues has blurred the frontier between noncancer and cancer clones.
Why the clones that accumulate with age do not generate cancers?
What is the molecular basis of cancer incidence increases with age beyond mutation-accumulation?
Clonal hematopoiesis is strongly associated with the acceleration of multiple aging-associated clocks.
How?
Unclear how processes such as stem cell competition for niche occupancy influence the switch from a premalignant to a malignant state.
It could help identify a sub-population at high risk of multiple aging-associated diseases and thus may be a target for clinical interventions.
What is the link between cell competition in aging epithelia and early steps of cancer?
For context: sciencedirect.com/science/articl…
What are the distinct paths for nonmalignant clones to transform into cancer?
What are the boundaries between a nonmalignant and a malignant clone?
Why do certain accelerated aging diseases increase cancer risk (Werner syndrome) vs. some decreases them (Hutchinson-Gilford progeria syndrome)?
Do people with germline mutations in cancer genes (RAS, BRCA1) have a different rate of the aging clock?
What is the ability of interventions to slow down aging effects to prevent cancer?
Five major intervention targets: Insulin growth factor pathway, the mammalian target of rapamycin (TOR) pathway, the family of sirtuins, the mitochondria and cells undergoing senescence.
What is the best approach to measure biological age in routine clinics? Can these measurements guide cancer treatment? Can changes in these measurements during therapy predict response?
What are the effects of cancer treatment on the aging of various tissues, including highly dividing tissues measured via multiple biological clocks measurements?
What are the links between biological age biomarkers and cancer risk?
Both the definition and our monitoring ability of senescent cells are poor.
How do you monitor and identify senescent cells in aging tissues?
How the efficacy of cellular therapy (CART, T-cell transfer therapy) is dependent on the patient's age?
Does it decrease due to immunosenescence and immune aging?
How the risk-benefit ratio for cancer treatment changes with age, and is there an inflection point?
Can combining senolytic drugs with existing cancer therapies affect the patient's response?
What is the role of pre-existing clonal hematopoiesis in frequently occurring therapy-related leukemia?
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