While it was widely anticipated that advances in endoscopic and ablative technologies applied to precursor lesions would spell the end of EAC and iGC, the rate of those who suffer from them has not appreciably decreased, and most patients still present with advanced disease and poor five-year survival.
This dire clinical reality has inspired a broad effort to understand the cell-of-origin of these diseases, their earliest emergence towards pathology, as well as their detection and pharmaceutical elimination.
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McKeon is the principal investigator on a new five-year, $4.7 million grant from the National Cancer Institute to advance this work. He’s joined on the research project by Wa Xian, research associate professor of biology and biochemistry at UH, and Dr. Jaffer Ajani MD of Anderson Cancer Center.
For over a decade, Xian has been perfecting technology for cloning stem cells and is fine tuning the technology to clone stem cells from the precursor lesions for these cancers.
“As all these lesions are still present in patients with advanced cancer, sequencing these patient-matched stem cells shows in exquisite detail the precise mutational changes that accompanied the evolution of the cancer,” said Xian.
Despite their emergence from disparate regions of the upper gastrointestinal tract, EAC and iGC show stunning similarities in their genetics and the precursor lesions in their evolution.
These markers have also enabled the cloning of the corresponding site-specific stem cells, which the team will do in both fetus and adult trials.
“We anticipate that our studies will provide new insights into the biology and origin of these remarkably similar and widespread cancers, provide datasets essential for prospective early detection screens and yield highly selective therapeutics that eliminate the nascent lesions essential for the evolution of these cancers,” said McKeon.
Source: Eurekalert
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