By 2030, pancreatic ductal adenocarcinoma (PDAC), the most lethal form of pancreatic cancer, is expected to become the second leading cause of cancer-related deaths in the United States. Therapeutic options are not only limited, but nearly half of all patients with PDAC whose tumors are removed experience a recurrence of the disease within a year, despite receiving additional chemotherapy. For more advanced stages, only about one-third of patients have a limited response to approved chemotherapy.
A team of researchers led by the director of the Norris Cotton Cancer Center (NCCC) in Dartmouth and Dartmouth-Hitchcock, Steven D. Leach, MD, and Surajit Dhara, Ph.D., a senior researcher at Leach Laboratory, in collaboration with colleagues at Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine are developing the first prognostic and therapeutic epigenetic biomarker for patients with PDAC.
Their findings will help predict which patients may or may not benefit from traditional chemotherapy. Patients with the possibility of “response” can be treated with confidence with traditional chemotherapy regimens, while patients with the possibility of “response” cannot receive an alternative regimen, potentially a combination of epigenetic therapy. Technology addresses an urgent clinical need by introducing the first approach to epigenetic precision medicine in the pancreas cancer, as a means to better outcomes and quality of life for all patients.
Epigenetic therapy can reactivate the expression of regulatory genes that have been silenced in chemotherapy-resistant tumors and thus make tumors sensitive to chemotherapy.
The team’s work, entitled “The prognosis of pancreatic cancer is predicted by ATAC-array technology to assess chromatin accessibility,” is recently published in Communications on Nature.
“We have a discovery and an invention that emanate from this work,” Dhara says. “By investigating all the epigenetic elements that regulate genes in PDAC, we found that only about 1,092 elements are associated with resistance to chemotherapy and early recurrence of this disease. Of these, 723 elements are silenced in tumors. chemo-resistant and are optimally predictive “.
To translate this knowledge into the clinic, Leach and Dhara invented a new technology platform called “ATAC-array” that evaluates gene regulatory elements as a means to predict chemotherapy response and potential benefit of epigenetic therapy in patients with PDAC. The technology is based on DNA and can potentially be performed on fine-needle aspiration samples collected from tumors at the time of diagnosis.
Although there are nine FDA-approved epigenetic drugs and many more in the pharmaceutical line, a fundamental means of distinguishing tumors that could benefit from epigenetic reprogramming therapy is still lacking. “It now appears that we are at the dawn of a new era in which epigenetic reprogramming is about to be increasingly relied upon to optimize therapeutic efficacy in multiple tumor “with this work,” says Leach, “we have pioneered a precision epigenetic approach in PDAC, a treatment approach that is already ready to be translated into the clinic.”
Leach and Dhara have co-founded Episteme Prognostics, Inc., a precision medicine company that develops therapeutic biomarkers for pancreatic cancer, in order to translate this work directly into the clinic as quickly as possible.
“The prognosis of pancreatic cancer is predicted by ATAC-array technology to assess chromatin accessibility.” Communications on Nature (2021). DOI: 10.1038 / s41467-021-23237-2
Dartmouth-Hitchcock Medical Center
Citation: Predicting Response to Chemotherapy and Adapting Treatments for Pancreatic Cancer Patients (2021, May 24) Retrieved May 24, 2021 at https://medicalxpress.com/news/2021-05-chemotherapy- response-tailoring-treatments-pancreatic.html
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