Induced viral mimicry is a way to get rid of cancer

Induced viral mimicry is a way to get rid of cancer ...

Researchers from Sanford Burnham Prebys received two grants, totaling $4.4 million, to study an emerging therapeutic method known as viral mimicry. Ancient endogenous retroviruses and retrotransposons in our genome (see grey box) are typically silenced. The awakening of these antiviral pathways inside the cell triggers an immune response and the cell is later targeted and destroyed.

Despite the fact that agents capable of inducing viral mimicry have previously been identified, they currently have one fatal flaw, an inability to distinguish between cancer cells and normal cells. Patients may also experience significant adverse effects.

Retrotransposons are genetic components that replicate via the reverse transcription of RNA. In this way, they can enliven the complementary DNA (cDNA) into new locations within a host cell genome.

Retroviruses from human origin are inherited genetic forms dating back to ancient infections that have occurred throughout the genome''s evolution. They constitute around 8 percent of the human genome and are classified as a type of retrotransposon.

Laura Lansdowne (LL): What benefits does viral mimicry offer over traditional cancer therapeutic strategies?

Many cancer therapies have side effects, according to Charles Spruck. The pathway FBXO44/SUV39H1, which is cancer cell specific, is very likely to have limited side effects for these drugs. Furthermore, viral mimicry has been shown to improve the appearance of other therapies.

One of the LL relatedgrant summaries that the FBXO44/SUV39H1 repetitive element silencing is an epigenetic vulnerability of cancer cells. Could you also know more about the FBXO44/SUV39H1 path?

CS: By mediating repressive H3K9me3 chromatin modifications, FBXO44 and SUV39H1 are not enriched at these elements in normal cells, but in cancer cells. This suggests that inhibiting the FBXO44/SUV39H1 pathway can be beneficial to reactivation of these elements and selective stimulation of antiviral pathways.

Can you elaborate on the two potential therapeutic applications of the FBXO44/SUV39H1 pathway targeting that you are planning to investigate?

CS: We are currently looking at various therapeutic applications for FBXO44/SUV39H1 involving drugs using preclinical mouse models. One is boosting immune response in estrogen receptor-positive breast cancer, which are basically resistant to immune checkpoint blockade therapy. We also found that FBXO44/SUV39H1 inhibition stimulates the stalling of DNA replication forks (also known replication stress) and we are looking at whether inhibition of the pathway can synergize with those clinics

Could this approach be applied to other types of cancer beyond breast cancer? If so, are there any particular cancers you are planning to investigate in the near future?

CS: We are currently looking at the pathway in cancers of the lung, the prostate, and the colon, as well as breast (both triple-negative breast cancer and ER+ breast cancer). So far, the results indicate that the pathway is required for these cancers.

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