ONJCRI researchers find that disruption of the GATOR1 gene complex promotes lymphoma development, opening the door to new therapeutic pathways
Researchers at the Olivia Newton-John Cancer Research Institute, WEHI (Walter and Eliza Hall Institute of Medical Research) and Peter MacCallum Cancer Centre have discovered genes which play a critical role in the prevention of lymphoma development.
Our DNA contains thousands of genes, each providing instructions to produce proteins that carry out essential functions in our body. The GATOR1 complex is a family of proteins encoded by specific genes.
The study, published in Nature Communications today, has identified the GATOR1 complex as an essential tumour suppressor, which could lead to new potential treatment targets for these common blood cancers.
The GATOR1 protein complex normally functions as a ‘brake’ on cell growth.1 When components of this protein complex are lost or defective, this protective mechanism fails, allowing cells to grow uncontrollably.
The team utilised sophisticated pre-clinical models of aggressive lymphoma to test the function of all known components in this complex. This revealed that when any of the GATOR1 genes are missing, lymphoma development is dramatically accelerated, identifying the GATOR1 complex as a crucial suppressor of blood cancer development.
Co-lead author Dr Margaret Potts said: “Our unbiased screening approach looked at all genes, rather than just a subset of them. By not limiting our investigation to known pathways, we found expected as well as unexpected tumour suppressor genes and pathways, such as GATOR1.”
Existing drugs that target the GATOR1 complex 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.
The researchers found that these drugs were highly effective at slowing the growth of lymphoma in pre-clinical models where components of the GATOR1 complex were missing.
“Our paper begins the exploration into this precision medicine opportunity,” shared Dr Potts.
Prof Marco Herold, CEO of ONJCRI and senior author of the Nature Communications paper, said:
“Our pre-clinical lymphoma model is driven by high levels of the gene MYC, an abnormality that can be found in ~70% of all human cancers. When GATOR1 is lacking, it removes a critical brake that normally slows MYC-driven cancer.
This exciting discovery provides a new insight into the development and sustained expansion of cancer, which we hope will underpin the development of more effective, targeted treatments for cancer.”
The research was led by Dr Margaret Potts, Dr Shinsuke Mizutani, and Dr Yexuan Deng, under the supervision of Prof Marco Herold, Prof Andreas Strasser (WEHI), and A/Prof Kristin Brown (Peter Mac).
According to the Global Cancer Observatory, there were over 630,000 new cases of lymphoma worldwide in 2022, highlighting the urgent need for a better understanding of the molecular mechanisms that drive this disease.2
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About the Olivia Newton-John Cancer Research Institute (ONJCRI)
ONJCRI is a global leader in advancing cancer research, driven by the singular goal of improving patient outcomes. We drive progress by discovering and developing diagnostics and therapeutics that are more effective, tolerable, and accessible.
ONJCRI adopts a tumour-agnostic approach, targeting shared pathways across multiple cancer types. This innovative strategy enables us to deliver scalable and impactful therapies that benefit diverse patient populations, accelerating progress across the entire landscape.
By bridging laboratory discoveries and clinical applications, ONJCRI is redefining how cancer treatments are designed and delivered: from bedside-to-bench-to-bedside. With a steadfast commitment to equity, innovation, and collaboration, we strive to transform cancer care, addressing unmet needs and overcoming disparities in access for all communities. For more about the Olivia Newton-John Cancer Research Institute, visit www.onjcri.org.au.
ONJCRI is an independent medical research institute and is affiliated with La Trobe University as the School of Cancer Medicine.
About WEHI (Walter and Eliza Hall Institute of Medical Research)
WEHI is where brilliant minds collaborate and innovate to make life-changing scientific discoveries that help people live healthier for longer. Our medical researchers have been serving the community for more than 100 years, making transformative discoveries in cancer, infection and immunity, and lifelong health. WEHI brings together diverse and creative people with different experience and expertise to solve some of the world’s most complex health problems. With partners across science, health, government, industry, and philanthropy, we are committed to long-term discovery, collaboration, and translation. At WEHI, we are brighter together. Find out more at www.wehi.edu.au
1 https://www.nature.com/articles/s41568-018-0074-8
2 https://gco.iarc.who.int/media/globocan/factsheets/cancers/33-hodgkin-lymphoma-fact-sheet.pdf, https://gco.iarc.who.int/media/globocan/factsheets/cancers/34-non-hodgkin-lymphoma-fact-sheet.pd