According to the Global Cancer Observatory, there were over 630,000 new cases of lymphoma worldwide in 2022, highlighting the urgent need for better understanding of the molecular mechanisms that drive this disease. Scientists already know that at least 70-80% of lymphoma cases rely on the activity of the proto-oncogene c-Myc and aberrations in regulators of the cell death pathway are well known to cooperate with over-expression of c-Myc in lymphoma onset. Therapeutic targeting of c-Myc is challenging for many reasons, including its involvement in regulating many essential cellular processes, such as cell cycling, proliferation, differentiation, metabolism and cell death. Therefore, understanding which processes are critical for Myc-driven oncogenesis might reveal downstream druggable cancer dependencies.
Australian researchers, a collaboration between the Olivia Newton-John Cancer Research Institute (ONJCRI), WEHI, and the Peter MacCallum Cancer Centre, have used an innovative genome-wide screening approach to identify genes, and their encoded proteins, that play critical roles in the prevention of lymphoma development, revealing new potential treatment targets for these blood cancers. The study, published in Nature Communications today, has identified a group of proteins known as the GATOR1 complex as essential tumor suppressors. The GATOR1 complex normally functions as a ‘brake’ on cellular growth by regulating pathways that control cell growth and metabolism. When GATOR1 components are lost or defective, this protective mechanism fails, allowing cells to grow uncontrollably.
The team utilized sophisticated pre-clinical models of aggressive lymphoma to systematically test the function of all known genes in this complex. Their comprehensive screening approach revealed that when any of the GATOR1 genes are lacking, lymphoma development is dramatically accelerated, identifying the GATOR1 complex as a cellular suppressor of blood cancer development. In other words, it is anti-oncogenic. Strikingly, existing drugs that target the same cellular pathways that GATOR1 typically controls, were highly effective at slowing the growth of lymphomas in GATOR1-deficient pre-clinical models. These drugs have previously had limited success in cancer treatment, and this may be because researchers have not been able to identify which patients would respond well to these therapeutics.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
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IMPaired 2 repair: how moonlightning is ultimately connecting metabolism to genomic stability (14/11/2024)
Lactate: that useless disposable junk, working as a genetic regulator in cancer cells
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Scientific references
Potts MA et al. Nature Commun. 2025 Aug; 16:7582.
Potts MA et al. Cell Death Differ. 2023; 30:1447-56.
Saxton RA, Sabatini DM. Cell 2017; 168:160–976.
