A collaborative effort which brought in researchers from many universities around the world reported finding common markers of tumor hypoxia among 19 cancer types. For their comprehensive study, the team analyzed mutation signatures of low oxygen in more than 8,000 samples.
In contrast to healthy tissue, tumors can continue developing even in low-oxygen conditions, often becoming treatment-resistant in the process and spreading to surrounding organs in the body. While it is known to cause metastasis and poor prognosis, the impact of low oxygen, or hypoxia, was never entirely understood. Now, clear signs of molecular changes of hypoxia have been determined with this first-ever pan-cancer study, which had a special focus on prostate malignancy.
“If we look at any single aspect of cancer, we only gain a partial understanding of this complex disease”, noted Vinayak Bhandari, lead author of this study and Ph.D. Candidate at the University of Toronto. “By tying together our new understanding of the environment in which tumours develop with detailed evaluation of genetic changes, we created a biological signature that highlights patients who may benefit from more therapy”.
Many of the samples were provided by the Canadian Prostate Cancer Genome Network (CPC-GENE). The newly discovered features could help predict cancer aggressiveness and inform treatment decisions. Findings include several key genes that are more frequently mutated in hypoxic cancers and new information about hypoxia-related patterns of disease evolution. All the information gathered was used to create the largest resource available for hypoxia research.
“Understanding common genomic traits across cancer types is critically important to the future of cancer diagnosis and treatment”, explained Dr. Paul Boutros, a professor at the University of California, Los Angeles, and senior investigator. “We were initially motivated by the inability to differentiate between aggressive and non-aggressive prostate cancers, but our findings provide insights into how treatments might be developed for many tumour types”.
The markers identified in the study open up new opportunities to develop therapies that specifically target hypoxia-related treatment resistance and metastasis across many types of cancer.
“We can now start to exploit these findings into novel clinical trials to target hypoxia and abnormal genetics at the same time”, added Professor Rob Bristow, Director at the Manchester Cancer Research and CRUK Manchester Centres.
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