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HIV Drug Found Effective In Metastatic Colorectal Cancer Treatment

Latest clinical research has shown that lamivudine, a reverse transcriptase inhibitor widely used in HIV therapy, could stop the spread of cancer in around 25 percent of patients with fourth-line metastatic colorectal cancer. The findings of the research were published in Cancer Discovery and offer new hope for treatment of not just colorectal cancer but also other forms of cancer as well.

The trial included 32 patients suffering from advanced metastatic colon cancer whose disease had spread in spite of four lines of earlier cancer treatments. The first nine patients received the standard HIV-approved dose of lamivudine. "After giving them only this one drug and nothing else, we saw signs of disease stability," says co-senior author David T. Ting, MD, of the Mass General Cancer Center. After adjusting the dosing four times more, another 23 patients received lamivudine therapy where it was highly tolerated.

The research team observed that 9 of the 32 patients, or 28 percent had disease stability or mixed response at the end of the trial. "This provides evidence that an HIV drug can be repurposed as an anti-cancer therapy in metastatic cancer patients," Ting added. While the research team did not see tumor shrinkage, the results were positive enough.

The first clues to this unusual drug trial were first seen in Ting's lab and his collaborators over the last ten years. The team discovered that up to 50 percent of a tumor's DNA was composed of "repetitive elements," which was earlier considered as "junk DNA." Colorectal cancers release large amounts of repetitive elements, as do cancers of the esophagus, lung, and several others. These repetitive elements bring out high levels of RNA, which replicate in a viral-like life cycle through reverse transcription into what Ting describes at the repeatome.

In their preclinical studies, Ting found that colorectal cancer cells were sensitive to lamivudine, reducing their ability to move. The team also found out that drug induced DNA damage and interferon responses is an indication that the drug led to an inflammatory response in the tumor cells. Although it was authorized in this trial, Ting found out that pairing reverse transcriptase inhibitor therapy with immunotherapy will encourage immune cells to become involved in these cancers.
Research has revealed that in a US population of HIV patients receiving three-drug anti-retroviral therapy for life, their incidences of colon, breast, and prostate cancer was less than the common public.

Ting feels that this kind of therapy might prevent a cancer or a recurrence or turn a crushing metastatic disease into a chronic disease like HIV.

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