
Experts from the Olivia Newton-John Cancer Research Institute, WEHI and Genentech have mapped genes that cause drug resistance in lymphoma treatment.
Using a next-generation CRISPR library called Partita, which activates all genes in the mouse genome, researchers mapped the genetic factors that cause treatment resistance in aggressive lymphoma and proved that the Irx5 gene inactivates the drug venetoclax.
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In cancer treatment, the development of resistance of cells to treatment is among the main biological problems that prevent success.
A critical threshold has been crossed in genetic research on the "treatment resistance development" mechanism, one of the biggest biological obstacles in the fight against cancer. Researchers from the Olivia Newton-John Cancer Research Institute (ONJCRI), WEHI and Genentech have introduced a next-generation CRISPR library called "Partita" that can activate all genes in the mouse genome one by one.
According to the study published in Science Advances, experts mapped the genetic factors that make targeted chemotherapy drugs ineffective in aggressive types of lymphoma.
IRX5 GENE INACTIVES SMART CANCER DRUG VENETOCLAX
In clinical trials, the protection shield developed by cancer cells against the active ingredient called "venetoclax", which is widely used in the treatment of blood cancer and lymphoma, was examined. Analyzes proved that with the activation of the Irx5 gene in the cell, cancerous structures silently produce a secondary protective protein and can escape the lethal effect of the drug.
Stating that traditional CRISPR technology only focuses on deleting genes, researchers report that thanks to the Partita system that activates the gene, all cellular actors that create resistance are detected and new compounds that will suppress these genes can be produced.
THREE HIDDEN GENES THAT ACCELERATE LYMPHOMA GROWTH WERE DETECTED
In their tests on live models, the research team also clearly identified genes that directly feed MYC-induced lymphoma, which is extremely difficult to treat, and accelerate its growth.
In the activation experiments, it was documented that tumor development accelerated when the Runx2, Runx3 and Csf1r genes were triggered. It was determined that the growth of cancerous tissue could be stopped if these genes were targeted and turned off.
NEW TREATMENT HOPE FOR THE MOST COMMON TYPE OF BLOOD CANCER IN ADULTS
It is aimed to prevent recurrences despite smart drugs and CAR T-cell treatments in cases of lymphoma, which is the most common in the adult population and has more than 80 subtypes.
Professor Marco Herold, Head of the School of Cancer Medicine at La Trobe University, declared that the genetic targets detected with Partita technology will multiply the effectiveness of existing cancer drugs and pave the way for a new generation of targeted combination therapies.

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