Surprising results show that a class of antiviral drugs blocks the progression of metastatic colorectal cancers that do not respond to any other treatment.
Cancers that reach an advanced stage are extremely difficult to treat, because they are made up of completely degenerated cells, where complete anarchy reigns within their chromosomes. Instead of the 23 pairs of chromosomes normally found in a healthy cell, cancer cells may contain 60 or even 90 chromosomes, some being present in multiple copies, while others are completely absent or formed randomly. from fragments from different chromosomes
Another frequently observed abnormality in the genetic material of cancer cells is the presence of large amounts of junk DNA (junk DNA), present as repetitive sequences.
Most of this junk DNA, which comes from ancient retroviruses that were integrated into the human genome during evolution, is dormant in normal cells but can become very abundant in certain types of cancer (colon, esophageal, and lung, among others). . In fact, the activation of these repetitive sequences generates large amounts of RNA that are subsequently replicated in DNA by an enzyme called reverse transcriptase present in some of these sequences of viral origin.
Repetitive DNA sequences are thus generated by a reproductive cycle that closely resembles that of retrovirus replication, leading to the accumulation of very large amounts of this DNA within cancer cells. Studies show that the activation of the immune system and the inflammatory response triggered by this reverse transcriptase-generated DNA are associated with an increased risk of metastasis.
Therefore, the interesting possibility arises that reverse transcriptase blockade by inhibitors commonly used against certain retroviruses (AIDS and hepatitis B viruses) may positively influence tumor progression and metastasis formation.
To test this possibility, a team of researchers from the Mass General Cancer Center (Boston) and the Memorial Sloan Kettering Cancer Center (New York) administered a reverse transcriptase inhibitor (lamivudine) to 32 patients with metastatic colorectal cancer resistant to all therapies. current1 . They found that despite the very poor prognosis of these patients, lamivudine produced a positive clinical response in 25%, with a median progression-free survival of 150 days (versus 60 for non-responders). One of the patients even reached 230 days of survival, which is remarkable considering the seriousness of the condition of these patients.
According to the authors, it is likely that the use of newer and more effective reverse transcriptase inhibitors could further improve this increase in survival.
Therefore, it seems that in certain types of cancer, the production of these repetitive DNA sequences plays an important role in the progression of these tumors and that the inhibition of the responsible enzyme, reverse transcriptase, could represent a new avenue of treatment. . These results would also explain why AIDS patients who are treated with therapies containing reverse transcriptase inhibitors have a reduced incidence of certain cancers, particularly those of the breast, prostate and colon2.
- 1. Rajurkar M et al. Reverse transcriptase inhibition disrupts repeat element life cycle in colorectal cancer. Discovery of cancer.published on March 23, 2022.
- 2. Coghill AE et al. Risk of breast, prostate, and colorectal cancer diagnoses among HIV-infected persons in the United States. National Cancer Institute J. 2018;110:959–966.
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