Summary
This Nature study elegantly shows the potential benefits of combining immunotherapy with PI3Kβ inhibitors in treating PTEN-deficient breast cancer and other types of PTEN-deficient cancers. The authors found that combination treatment resulted in a synergistic suppression of tumor growth and the development of immune memory, which could be a promising therapeutic avenue for these cancers if the results are replicated in humans.
What is the PTEN Pathway?
PTEN (phosphatase and TENsin homolog deleted) mutations or altered functions appear in approximately 13.5% of human cancers, making it one of the most common drivers of cancer across all types. One of PTEN’s major functions is blocking PI3K signaling, a signaling pathway that promotes cell growth and differentiation.
PI3K signaling has been shown to play an important role in PTEN-deficient breast tumors, due to the lack of regulation of the pathway allowing for dysregulated growth. Interestingly, the PI3Kβ isoform seems particularly involved, but the mechanism it works through has remained unclear.
PI3Kβ Inhibition Promotes Anti-Tumor Responses
In a recent paper in Nature, Bergholz et. al. investigated the mechanism of action of PI3Kβ inhibition in PTEN and p53-null mice with invasive breast cancer. When PI3Kβ was genetically inhibited, the authors observed a robust anti-tumor response in mice with functional immune systems, but not in immunodeficient mice.
The response appears to be mediated by reduced STAT3 signaling and an increase in immune stimulatory molecules, which work synergistically to promote anti-tumor responses. The response thus is dependent on a functional immune system, explaining the lack of effect in the immunodeficient mice.
Immunotherapy and PI3Kβ Inhibition Combination Treatment
The authors observed that in addition to genetic inhibition of PI3Kβ, pharmacological inhibition of PI3Kβ produced anti-tumor immunity. In combination with immunotherapy, a synergistic suppression of tumor growth and a level of immune memory were displayed in the combination treated mice.
These results are a promising therapeutic avenue for PTEN-deficient breast cancer and potentially other PTEN-deficient cancer types. Combining existing immunotherapy with PI3Kβ inhibitors, with the underlying molecular mechanism to explain them, could be a valuable treatment strategy if it is effective in humans as it was in mice.
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Jane Cook, Biochemist & Content Writer, Bridge Informatics
Jane Cook, leading Content Writer for Bridge Informatics, has written over 100 articles on the latest topics and trends for the bioinformatics community. Jane’s broad and deep interdisciplinary molecular biology experience spans developing biochemistry assays to genomics. Prior to joining Bridge, Jane held research assistant roles in biochemistry research labs across a variety of therapeutic areas. While obtaining her B.A. in Biochemistry from Trinity College in Dublin, Ireland, Jane also studied journalism at New York University’s Arthur L. Carter Journalism Institute. As a native Texan, she embraces any challenge that comes her way. Jane hails from Dallas but returns to Ireland any and every chance she gets. If you’re interested in reaching out, please email jennifer.martinez@old.bridgeinformatics.com or dan.ryder@old.bridgeinformatics.com.
