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Common Markers of Tumor Hypoxia Found Across Cancer Types

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Key Points

  • In 10 of 19 tumor types, hypoxia was associated with elevated genomic instability. In all 19, tumors classified as hypoxic exhibited driver-mutation signatures.
  • Hypoxia was associated with dysregulation of microRNAs across cancer types. Researchers validated miR-133a-3p as a hypoxia-modulated miRNA. 
  • In localized prostate cancer specifically, hypoxia was linked to higher rates of chromothripsis (multiple chromosomal rearrangements), allelic loss of PTEN, and shorter telomeres.

Unlike healthy tissues, tumors thrive in low-oxygen environments, often acquiring the ability to resist treatment and spread to other sites in the body. Despite being a well-known cause of therapy resistance and metastasis, the impact of hypoxia on tumor cells is poorly understood. Researchers have discovered molecular hallmarks of hypoxia in the first-ever pan-cancer analysis of low oxygen in human tumors, with a special focus on prostate cancer. Their findings were published by Bhandari et al in Nature Genetics.

The study investigated more than 8,000 human tumors across 19 different cancer types, including prostate tumors from the Canadian Prostate Cancer Genome Network (CPC-GENE). The authors discovered common markers of hypoxia that could help predict cancer aggressiveness and inform treatment decisions.

Study Findings

In 10 of 19 tumor types, hypoxia was associated with elevated genomic instability. In all 19, tumors classified as hypoxic exhibited driver-mutation signatures. Researchers also found that hypoxia was associated with dysregulation of microRNAs across cancer types and validated miR-133a-3p as a hypoxia-modulated miRNA. In localized prostate cancer specifically, hypoxia was linked to higher rates of chromothripsis (multiple chromosomal rearrangements), allelic loss of PTEN, and shorter telomeres.

The markers observed in this study open new opportunities for researchers to develop therapies that target hypoxia-related treatment resistance and metastasis across many types of cancer, including prostate cancer.

“If we look at any single aspect of cancer, we only gain a partial understanding of this complex disease. But here we’ve exploited a wealth of human tumor data to gain a more comprehensive understanding,” said Vinayak Bhandari, lead author of this study and a PhD candidate at the University of Toronto who is also conducting research at the Ontario Institute for Cancer Research. “By tying together our new understanding of the environment in which tumors develop with detailed evaluation of genetic changes, we created a biological signature that highlights patients who may benefit from more therapy.”

“Understanding common genomic traits across cancer types is critically important to the future of cancer diagnosis and treatment,” said senior author Paul Boutros, PhD, of the University of California, Los Angeles. “We were initially motivated by the inability to differentiate between aggressive and nonaggressive prostate cancers, but our findings provide insights into how treatments might be developed for many tumor types.”

Disclosure: The study was supported by the Movember Foundation, Prostate Cancer Canada, the Ontario Institute for Cancer Research through CPC-GENE, and the Terry Fox Research Institute. The study authors’ full disclosures can be found at nature.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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