A New Path to Tumor Suppression: The Promise of PG3

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Dec 18, 2024

The discussion centers on a revolutionary compound, PG3, which has the potential to treat resistant cancers without depending on the often-mutated p53 protein. Researchers highlight the groundbreaking approach of activating the integrated stress response pathway to restore tumor suppression. This innovative therapy promises a new era in personalized cancer care, offering hope for aggressive cancer treatment. The findings could redefine strategies in oncology, especially for patients with p53 mutations.

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INSIGHT

P53's Importance and Mutation Prevalence

P53, the "guardian of the genome," is crucial for cancer prevention.
However, it's mutated in about half of all cancers, rendering it ineffective.

INSIGHT

PG3: A New Path to Tumor Suppression

PG3 is a novel compound restoring tumor suppression without relying on p53.
It offers a new treatment option for resistant cancers, unlike p53-targeted therapies.

INSIGHT

PG3's Mechanism of Action

PG3 activates HRI kinase, initiating the integrated stress response (ISR).
This activates ATF4, which triggers tumor-suppressing genes like PUMA and P21, inducing apoptosis.

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The p53 protein, often called the “guardian of the genome,” is crucial for preventing cancer by repairing damaged DNA or triggering cell death in cells that cannot be repaired. However, in about half of all cancers, the p53 gene is mutated, making the protein ineffective. A groundbreaking study has introduced PG3, a new compound that restores tumor suppression without relying on p53, offering a new option to treat resistant cancers. Published in Oncotarget on September 17, 2024, the study titled “Integrated stress response (ISR) activation and apoptosis through HRI kinase by PG3 and other p53 pathway-restoring cancer therapeutics,” introduces PG3, a small molecule with a completely new approach to treating cancer. This groundbreaking research was conducted by Dr. Xiaobing Tian and Oncotarget Editor-in-Chief Dr. Wafik S. El-Deiry from Brown University. The researchers tested PG3 on cancer cell lines with various p53 mutations, as well as on cells that lacked p53 entirely. Full blog - https://www.oncotarget.org/2024/12/18/a-new-path-to-tumor-suppression-the-promise-of-pg3/ Paper DOI - https://doi.org/10.18632/oncotarget.28637 Correspondence to - Wafik S. El-Deiry - wafik@brown.edu Video short - https://www.youtube.com/watch?v=eBp_UGrkii8 Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28637 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, mutant p53, integrated stress response (ISR), ATF4, HRI, ClpP About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science). To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM