Blocking the survival system of cancer cells could tackle melanoma treatment resistance, scientists have said.
Researchers from the Babraham Institute, AstraZeneca and the Cancer Research UK Cambridge Centre have found a method – used in conjunction with existing treatments – which knocks out one of melanoma cells’ survival pathways.
They say it is effective at triggering tumour cell death and delaying treatment resistance in the deadliest form of skin cancer.
The scientists suggest this approach may also help to tackle late stage cancers, even after they have become resistant to existing treatments.
Lead researcher Dr Mathew Sale, from the Babraham Institute, said: “This study has demonstrated that melanoma cells are addicted to the MCL1 protein for survival, but only when they are treated with the existing melanoma drugs.
“By targeting both vulnerabilities at the same time we can kill melanoma cells, causing greater inhibition of tumour growth over a longer time period.”
Cancer cells can rely on various “survival proteins” to stay alive despite the effect of treatment.
So far researchers have not been able to isolate which of these proteins are used by melanoma cells, but the study published in Nature Communications found that melanoma cells rely on a protein called MCL1.
This is critical for the cells to survive when exposed to standard drugs that inhibit the MEK and BRAF proteins, such as trametinib or vemurafenib.
Researchers then studied an investigational compound from pharmaceutical company AstraZeneca, an MCL1 antagonist called AZD5991, and used it in the lab against models of melanoma.
They showed that by blocking MCL1, the agent inactivated the back-up survival system in melanoma cells.
Combining it with a treatment like vemurafenib had a double effect against cancer cells, eliminating them more effectively.
The drug combination also worked by reducing, or sometimes eliminating, melanoma tumours derived from patients and grown in mice.
Used alone, the agent had no effect in these models.
Dr Simon Cook, group leader at the Babraham Institute, said: “This study stems from 15 years of basic research in which we have sought to understand the normal signals that control whether a cell lives or dies.
“However, we became increasingly aware that these same pathways were not functioning correctly in cancer.
“Thanks to a long-standing partnership with AstraZeneca and the Cancer Research UK Cambridge Centre we were able to translate this basic research to understand and potentially better treat melanoma.”