The introduction of HAART (highly active anti-retroviral therapy) in the mid-1990s revolutionized the treatment of HIV/AIDS, halting disease progression and dramatically extending lives.
Now, a small new study suggests another potential use for one of the standard HAART medications: It halted disease progression in about a quarter of patients who were battling advanced colon cancer.
“What is most surprising is that this is a class of drugs we have used effectively for viruses for many years,” said study author Dr. David Ting. “And now this study opens the opportunity to develop this class of drugs for cancer.
“We are still trying to understand why some patients might benefit more than others,” said Ting, who serves as director of the Tumor Cartography Center at Massachusetts General Hospital Cancer Center in Boston.
While acknowledging that more research will be needed, Ting described the findings as “exciting,” adding that beyond colon cancer it appears likely that “this [drug] strategy may be effective across multiple cancer types.”
Ting noted that HAART treatment for HIV patients — which is typically administered as a combination of several medications — targets specific proteins called “reverse transcriptases” (RT).
That’s because HIV needs RTs to replicate and spread.
“[But] we and others have previously found that RT proteins in human cells are reactivated in cancer,” explained Ting, also an associate professor of medicine with Harvard Medical School. “Therefore, these RT drugs for HIV [also] have the ability to block these human RTs found in cancer.”
To underscore that point, Ting highlighted a 2018 research paper that found that patients living with HIV while undergoing a three-drug “cocktail” of HAART therapy do, in fact, tend to have a significantly lower incidence of many types of cancer than the general population. That lower risk, researchers found, includes breast, prostate and colon cancer.
For the new study, Ting and his colleagues explored the potential of just one widely used HAART medication: lamivudine.
The trial involved 32 patients, all of whom were diagnosed with advanced colon cancer that had spread widely, despite a series of standard but unsuccessful cancer treatments.
Ultimately, all the patients were given lamivudine, but at notably higher doses — approaching 400% more — than is typically given to HIV patients. (HAART medications are known to be “well-tolerated” among HIV patients, said Ting, though he cautioned that it remains to be seen whether higher doses might give rise to new side effects.)
Lamivudine was administered without any other form of cancer therapy. The result, Ting noted, was that eight of the patients saw the progression of their cancer come to a halt, while one more achieved a “mixed response.”
None of the patients saw their tumors shrink. But the team did observe encouraging “biological changes in the tumors when we looked at biopsies before and after treatment,” Ting said.
The findings were published recently in the journal Cancer Discovery.
The progression-halting impact that the HAART med appeared to have on colon cancer suggests that “tumors behave in virus-like ways,” said study co-author Benjamin Greenbaum, an associate attending in the computational oncology service at Memorial Sloan Kettering Cancer Center in New York City.
In fact, Greenbaum said, lamivudine’s impact on tumor cells is so similar to its impact on HIV that it amounts to a “surprising” form of “viral mimicry.”
Still, the majority of patients did not appear to reap any benefit. Ting suggested that in theory it might be because of differing amounts of RT proteins found in the cancer cells of individual patients.
“We are…trying to better understand which cancers are more dependent on this RT activity, so that we can have more precision in the patients that might benefit from this therapy,” he said, stressing that the prospects for this type of cancer intervention “are still in the early days.”
Even so, Dr. Andrew Chan — a professor in the department of medicine at Harvard Medical School and vice chair of gastroenterology at Massachusetts General Hospital — said that the possibility of using HAART meds to treat advanced cancer would “represent a new target for treatment, which is really exciting, especially if we can repurpose existing drugs for other conditions for which we have a wealth of clinical experience.”
There’s more on the connection between HIV and cancer risk at the U.S. National Cancer Institute.
SOURCES: David Ting, MD, associate clinical director, innovation and director, Tumor Cartography Center, Massachusetts General Hospital Cancer Center, and associate professor, medicine, Harvard Medical School, Boston; Benjamin Greenbaum, PhD, associate attending, computational oncology service, Memorial Sloan Kettering Cancer Center, New York City; Andrew Chan, MD, MPH, professor, department of medicine, Harvard Medical School and vice chair, gastroenterology, Massachusetts General Hospital; Cancer Discovery, March 23, 2022
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