Ibrutinib Repurposed for Esophageal Cancer Treatment

Researchers have found a novel way to kill esophageal cancer cells by repurposing a drug approved to treat blood cancer. A new study published by Gut suggests that esophageal cancer cells may be particularly sensitive to ibrutinib (Imbruvica).

In the study, the authors discovered that esophageal cancer cells with a cancer-causing MYC gene mutation resulted in the cells becoming dependent on the BTK gene. By inhibiting BTK with ibrutinib, the authors killed lab-grown cancer cells without affecting healthy cells.

Attacking esophageal cancer cells dependent on BTK—known as synthetic lethality—may open up options for patients whose treatments are currently limited, according to the study.

“The DNA of cancer cells tends to be extremely mutated — whilst these mutations cause cancer, they also often make cells addicted to genes normal cells are not,” said researcher Chris Lord, DPhil. “Finding which genes cancers are addicted to is an exciting approach for identifying new ways of attacking tumours [sic]. We can now systematically identify genes which cancer cells need but healthy cells can live without – offering up the potential of precision therapies that have fewer side-effects than conventional treatments.”

To identify the dependence, the investigators assessed the sensitivity of esophageal cancer cells to drugs that are currently used to treat other forms of the disease, according to the study. The authors also explored the effects of inactivating 720 key genes on cancer cells.

By incorporating both approaches, the researchers discovered the association between BTK dependence and sensitivity to ibrutinib in esophageal cancer cells.

The investigators harnessed this information to design a clinical trial and have also made their findings public so that other researchers can use the data.

The authors are currently exploring whether ibrutinib will be effective in patients with esophageal cancer with MYC mutations in a phase 2 clinical trial, according to the study.

“Our new study has identified a potential Achilles’ heel in some forms of oesophageal [sic] cancer, which we believe could be exploited by new treatments,” said researcher Irene Chong, PhD. “And because there is an existing drug for other forms of cancer which attacks this weakness, we can test out our new approach rapidly in clinical trials.”

If proven in humans, ibrutinib may expand therapy to many patients with esophageal cancer, which is known to be particularly aggressive with limited treatment options.

“If clinical trials show that this drug is effective, this work could lead to a new treatment for some oesophageal [sic] cancer patients, which is urgently needed for this hard-to-treat disease,” said Karen Vousden, PhD, chief scientist at Cancer Research UK.