Thursday, April 07, 2022

HIV drug stabilizes progression in metastatic colorectal cancer

Amazing stuff! Cancer is history soon! Perhaps, these results open up a new direction in research!

"Findings from the trial, published in Cancer Discovery, raise the possibility of an unexpected promising direction in cancer treatment, not just colorectal cancer. The drug used in the study was lamivudine, a reverse transcriptase inhibitor.
The trial included 32 patients with advanced metastatic colon cancer whose disease progressed despite four lines of previous cancer treatments. The first nine patients received the standard HIV-approved dose of lamivudine.
“After giving them only this one drug — nothing else — we saw signs of disease stability,” ... After adjusting the dosing four-fold, 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,” ... did not see tumor shrinkage, the results are encouraging. ...
The first clues to this unusual drug trial surfaced in Ting’s lab and those of his collaborators over the past 10 years. The team discovered that up to 50 percent of a tumor’s DNA was composed of “repetitive elements,” which were previously considered “junk DNA.” ...
Only cancer cells produced these repetitive element, not healthy cells,” ... Colorectal cancers produce abundant amounts of repetitive elements, as do cancers of the esophagus, lung, and several others. These repetitive elements spew out extraordinary levels of RNA which replicate in a viral-like life cycle through reverse transcription ..."

From the abstract:
"Altered RNA expression of repetitive sequences and retrotransposition are frequently seen in colorectal cancer (CRC) implicating a functional importance of repeat activity in cancer progression. We show the nucleoside reverse transcriptase inhibitor 3TC targets activities of these repeat elements in CRC pre-clinical models with a preferential effect in P53 mutant cell lines linked with direct binding of P53 to repeat elements. We translate these findings to a human Phase 2 trial of single agent 3TC treatment in metastatic CRC with demonstration of clinical benefit in 9 of 32 patients. Analysis of 3TC effects on CRC tumorspheres demonstrates accumulation of immunogenic RNA:DNA hybrids linked with induction of interferon response genes and DNA damage response. Epigenetic and DNA damaging agents induce repeat RNAs and have enhanced cytotoxicity with 3TC. These findings identify a vulnerability in CRC by targeting the viral mimicry of repeat elements."

HIV drug stabilizes progression in metastatic colorectal cancer – Harvard Gazette Stabilized 25 percent of patients in trial by disrupting the repeat element in life cycle of disease

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