Reverse Transcriptase Inhibitors Used in HIV Therapies Stop Disease Progression in Metastatic Colorectal Cancer

New research published in Cancer Discovery found an HIV drug used in treatment therapies, known as Iamivudine, stops disease progression in 25 percent of patients with fourth-line metastatic colorectal cancer. Past research from the National Center for Biotechnology Information found HIV patients receiving lifelong three-drug anti-retroviral therapy had a notably lower risk of colon, breast, and prostate cancer. Dr. David T. Ting, MD, of the Mass General Cancer Center, theorizes this type of therapy might prevent cancer, recurrence, or turn a metastatic disease into something more chronic like HIV.

In preclinical studies, Dr. Ting and his team observed colorectal cancer cells were sensitive to Iamvudine, reducing their movement, and found drug-induced DNA damage and interferon responses—proving Iamvudine triggered inflammatory responses in tumor cells. The researchers found that 50 percent of a tumor’s DNA were made of “repetitive elements”—seen in esophagus, lung, and several other types of cancer—that weren’t present in healthy cells. High levels of RNA reproduce in a viral-like cycle known as “repeatome,” which relies on reverse transcription to move. Dr. Ting theorizes that immunotherapy joined with reverse transcriptase inhibitor therapy might help immune cells become more involved against cancers.

Thirty-two patients whose disease had progressed despite four lines of previous cancer treatments were identified. The first nine received a standard HIV-approved dose of Iamvudine and another 23 received a dose that was adjusted to four times the original dose. Just one dose produced significant signs of disease stability, with nine of the 32 patients (28 percent) showing stability or a mixed response.

“This provides evidence that an HIV drug can be repurposed as an anti-cancer therapy in metastatic cancer patients,” Dr. Ting says. “We did the trial to see if we could learn something new about the biology of cancer cells and in the process found this unexpected, very encouraging result. Disease stability in a cancer patient population this advanced, with just one single agent, is highly unusual and we are hoping we can soon initiate a larger Phase III study with a three-drug reverse transcriptase inhibitor combination.”