Senescent cells fuel blood vessel growth in bowel cancer
In bowel cancer, senescent cells in the surrounding tissue help tumours grow new blood vessels. That makes certain tumours harder to treat than previously thought.
When cells become senescent, they stop dividing but do not disappear. Instead, they secrete a mix of proteins and signalling molecules that alter the cell’s environment. This phenomenon is called the senescence-associated secretory phenotype (SASP). Researchers published a review in the journal Aging Cell examining SASP’s role in colitis-associated cancer (CAC), a form of bowel cancer that develops from chronic intestinal inflammation.
More blood vessels, less response to standard treatment
SASP promotes the formation of new blood vessels (angiogenesis). These vessels supply growing tumours with oxygen and nutrients. Standard treatments target a growth factor called VEGF to block this process. But the researchers show that in CAC, blood vessel growth is driven by a broad and redundant set of factors sustained by inflammation and tissue injury. VEGF-targeted treatments may be less effective against this.
The study also distinguishes CAC from sporadic colorectal cancer (CRC). In CRC, development follows a different pathway in which certain gene mutations occur later. In CAC, mutations in the tumour suppressor gene TP53 occur early, while other cancer-related mutations follow later. That sequence reflects the pressure that chronic inflammation places on intestinal tissue.
Aging amplifies risk through multiple pathways
Aging contributes to this process in several ways. More cells in gut tissue become senescent as people age. Aging also alters the gut tissue environment, making malignant growth easier to initiate. SASP increases both inflammation and the formation of connective tissue (fibrosis), two processes that independently raise cancer risk.
This is a review study: the authors discuss existing literature and formulate hypotheses. The findings provide a framework for further research into senolytics (drugs that clear senescent cells) as a possible addition to bowel cancer therapy, but the researchers themselves regard that as hypothetical for now.