Mitochondria Engage the Integrated Stress Response to Promote Tumor Growth

“Overall, this research proposes a new paradigm on how AR-independent PCa can drive tumor traits by exploiting mitochondrial signaling pathways [...]” 

BUFFALO, NY- March 8, 2023 – A new editorial paper was published in Oncotarget's Volume 14 on February 25, 2023, entitled, “Mitochondria engage the integrated stress response to promote tumor growth.”

In this new editorial, researchers Dillon P. Boulton and M. Cecilia Caino from the University of Colorado School of Medicine discussed prostate cancer (PCa)—the most diagnosed and second deadliest cancer among men in the United States, with an estimated 268,490 new cases and 34,500 deaths in 2022 (ACS Cancer Facts and Figures 2022). 

“While the prognosis for men with early-stage disease remains extremely favorable (>99% 5-year overall survival, OS), men diagnosed with metastatic PCa have a 30% 5-year OS, clearly demonstrating a need for therapeutic options for these patients (ACS Cancer Facts and Figures 2022).”

Due to a strong reliance on androgens to drive PCa, first and second courses of therapy involve androgen deprivation therapy or targeting the androgen receptor directly in combination with several other cytotoxic agents [1–3]. Unfortunately, some tumors develop resistance to these androgen axis therapies and progress to castrate resistant and metastatic PCa, which drives the majority of PCa deaths. This underscores a strong need to identify and characterize actionable targets within these tumors. Of interest, mitochondria are emerging as critical organelles that promote tumorigenesis and metastasis.

“​​Along this line, we have recently described a novel signaling pathway where mitochondria promote castrate resistant metastatic PCa growth by acting as a signaling platform to facilitate efficient stress signaling [11]. This pathway is centered around mitochondrial Rho GTPase 2 (MIRO2), an outer-mitochondrial membrane protein in the Ras superfamily of GTPases [12, 13].”

Read the full editorial: DOI: https://doi.org/10.18632/oncotarget.28372 

Correspondence to: M. Cecilia Caino

Email: Cecilia.caino@cuanschutz.edu 

Keywords: mitochondria, prostate cancer, integrated stress response

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.

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