New preclinical evidence suggests a key cellular stress response pathway could be a promising therapeutic target for multiple myeloma.
Researchers at The Institute of Cancer Research, London, say that targeting a protein called heat shock factor 1 (HSF1) has been effective in reducing survival of multiple myeloma cells in vitro.
The Cancer Research UK funded study, published in the latest edition of Clinical Cancer Research, first analysed genetic information from more than 250 people with myeloma and found that increased HSF1 gene activity was related to poor patient outcome.
HSF1 is a regulator of the cellular stress response - boosting a cell’s ability to cope under compromised conditions. By genetically targeting this stress-buffering system in the cancer cells, the team were able to weaken this defence mechanism and reduce their capacity for survival.
The team then treated myeloma cells with two prototype drugs designed to block the HSF1 pathway - both inhibitors killed a substantial proportion of the cancerous cells.
When combined with bortezomib, an established anti-cancer drug, both HSF1 inhibitors enhanced its effect, they reported. The inhibitors also caused some death of healthy cells - but to a lesser extent than in myeloma, they report.
Study co-lead Professor Paul Workman, chief executive of The Institute of Cancer Research said: “We hope that HSF1 pathway inhibitors could offer a potential new and much needed way to treat myeloma. The next stage will be to start testing the new treatment approach in patients in early-phase clinical trials.
“If we’re going to deliver step-change improvements for cancer patients, we need to find brand new ways of attacking cancers. Blocking cancer’s ability to cope with stress is one such innovative idea, and our study shows that it offers real promise. I’m excited to see this new approach to treatment assessed in cancer patients as soon as possible.”
Professor Karen Vousden, Cancer Research UK’s Chief Scientist, added: “This study’s identification of a new way to kill myeloma cells is a step towards improving the outlook for people with this cancer.”
The research team now plans to carry out clinical studies on HSF1 and to further investigate the benefits of combination therapy with bortezomib.
Source: Fok et al. HSF1 Is Essential for Myeloma Cell Survival and A Promising Therapeutic Target. Clinical Cancer Research 1 February 2018; doi: 10.1158/1078-0432.CCR-17-1594
Link: http://clincancerres.aacrjournals.org/content/early/2018/01/30/1078-0432.CCR-17-1594
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