Can chemotherapy make cancer progression worse?

Chemo may kill cancer cells, but it also causes senescent cells to be made; it now seems that these can drive cancer spread throughout the body.

Senescent cancer cells - a double edged sword 

When cancer patients with tumours have chemotherapy, not all the cancer cells are killed. Some cancer cells experience senescence and this has been known for a number of years with the original view that these cells were weak and feeble. Senescent cancer cells are damaged cells that stop multiplying through a permanent cell cycle arrest. Hitherto, this was seen as a double edged sword. On one side these cells cells lower tumour growth, but at the same time they can promote inflammation and treatment resistance.

But here’s the new  problem. They may have stopped dividing but senescent cells actually can secrete an array of factors, collectively known as the senescence-associated secretory phenotype (SASP). And it now appears that these secretions can even cause cancer cells to scatter and spread from the tumour. 

In a recent research study (1), which looked at High Grade Serous Ovarian Cancer (HGSOC), both in vitro and in vivo, with a platinum based drug (normally Carboplatin, but here Cisplatin), these senescence factors were shown to cause detachment of the tumour cells in vitro, and dissemination throughout the body in vivo. 

Common sugar, fructose, the driver?

One metabolic factor in particular in the SASP was Fructose. Chemotherapy-surviving senescent cancer cells release fructose as a signaling molecule.  

Now we already know that high-fructose corn syrup (also called glucose-fructose syrup) has previously been shown to cause and drive cancer more than ordinary glucose. HFCS is common in many soft and fizzy drinks. 

In this study, the researchers attributed the widespread scatter caused by the senescent cells to this common sugar.  

Researchers showed clearly that in the cisplatin-induced SASP patients fructose was the metabolic component that facilitated cell detachment in vitro and a high-fructose diet increased HGSOC dissemination in vivo. 

Many press stories focussed on the fructose sugar driving the cancer, but make up your own mind.

Do platinum-based drugs cause the cancer to scatter in Ovarian cancer?

The researchers said ‘Yes’. Indeed the first line of the research results stated that ‘the cisplatin-induced SASP promotes HGSOC dissemination in vivo’. 

Researchers also stated that the majority of High Grade Serous Ovarian cancer patients initially treated with platinum drugs often see recurrence with widespread disseminated disease, causing shorter disease-free survival.  This has been noted before (2)

The amount of the spread, according to the researchers, depends on the drug used.

This should alarm everybody having chemo. 

References

1.  The chemotherapy-induced senescence-associated secretome promotes cell detachment and metastatic dissemination through metabolic reprogramming; Cole, A.R., Buj, R., Uboveja, A. et al; Nat Aging (2026). https://doi.org/10.1038/s43587-026-01172-5

2. The capacity of the ovarian cancer tumor microenvironment to integrate inflammation signaling conveys a shorter disease-free interval; Jordan, K. R. et al.  Clin. Cancer Res. 26, 6362–6373 (2020).