Can One Drug Tackle Both Cancer and Ageing?
Ageing and cancer are often treated as separate biological problems, but at the cellular level they are closely intertwined. One key link is cellular senescence—a state in which damaged cells stop dividing but remain metabolically active. While senescence can suppress tumours early on, senescent cells accumulate with age and release inflammatory signals that can actually promote cancer growth. This paradox is especially relevant in the liver, where chronic inflammation, fibrosis, and ageing all raise the risk of hepatocellular carcinoma (HCC), the most common form of liver cancer.
In a new study published in npj Aging, researchers used artificial intelligence to search for molecular weak points shared by both liver cancer and cellular senescence. Their goal: identify dual-purpose drug targets that could slow ageing-related tissue damage while also suppressing tumour growth.
Using AI to Hunt for Shared Targets
The team analysed data from 1,047 liver cancer samples and 563 healthy controls across 11 independent datasets. They fed this information into PandaOmics, an AI-powered platform that integrates genomics, gene expression, protein interaction networks, and biomedical literature.
From an initial pool of hundreds of genes linked to senescence, the algorithm narrowed the field to 49 high-confidence or novel candidates associated with both senescence pathways and HCC. Further filtering—based on consistency across datasets and druggability—highlighted two standout genes: PRPF19 and MAPK9.
PRPF19: Selectively Clearing Senescent Cells
To test PRPF19’s role, the researchers induced senescence in human hepatic stellate cells using 25 nanomolar doxorubicin, a dose that reliably triggered senescence without killing the cells. Knocking down PRPF19 using siRNA had a striking effect.
Compared with untreated senescent cells, PRPF19 suppression significantly reduced the proportion of senescent cells, as measured by senescence-associated β-galactosidase staining. Importantly, this effect resembled that of navitoclax (ABT-263), a well-known senolytic drug—but without causing comparable toxicity in healthy cells.
RNA sequencing revealed why. PRPF19 knockdown led to strong reductions in key components of the senescence-associated secretory phenotype (SASP)—the inflammatory cocktail that senescent cells release. Several SASP genes were downregulated with high statistical significance (adjusted p < 0.01 to < 0.0001), suggesting PRPF19 helps maintain the harmful inflammatory environment created by ageing cells.
MAPK9: Slowing Tumour Growth and Senescence
The second key target, MAPK9, showed promise on two fronts. When MAPK9 was silenced in multiple liver cancer cell lines—including Huh-7, Hep-G2, and MHCC97H—cell proliferation dropped sharply. Colony formation assays confirmed that MAPK9 knockdown significantly reduced tumour cell growth, while Ki-67 staining showed fewer actively dividing cells.
At the same time, MAPK9 suppression also reduced senescent cell burden, marking it as a “senomorphic” target—one that dampens the harmful effects of senescence without necessarily killing senescent cells outright.
Crucially, MAPK9 is part of the MAP kinase family, a signalling pathway already targeted by approved cancer drugs. This raises the possibility of drug repurposing. Existing MAPK inhibitors, such as encorafenib, could potentially be adapted to treat HCC while also mitigating age-related inflammation in the liver.
Why This Matters
Hepatocellular carcinoma is notoriously difficult to treat, with five-year survival rates often below 20%. At the same time, ageing populations are driving up rates of chronic liver disease. This study suggests that targeting shared molecular drivers of ageing and cancer could yield more durable and systemic benefits than tumour-focused therapies alone.
By reducing senescent cell accumulation, dual-purpose therapies may also improve liver metabolism, immune function, and tissue repair—factors that influence overall resilience in older patients.
A New Direction for Age-Informed Cancer Therapy
The study highlights the growing role of AI in biomedical discovery, not just for finding new drugs, but for rethinking disease boundaries. Instead of treating cancer and ageing as separate problems, the work points toward therapies that address their common roots.
While the findings are still preclinical, PRPF19 and MAPK9 now stand out as promising targets for future drug development—and as proof that the biology of ageing may hold untapped solutions for cancer treatment.
The study is published in the journal npj aging. It was led by Alex Zhavoronkov from Insilico Medicine, Hong Kong, China.
