part of a Special Report by Duke Cancer Institute & the Department of Pathology, Duke University School of Medicine — as featured in the 2021-22 Department of Pathology Annual Report (pdf)
Oncologists today have a wider range of anti-cancer drugs to reach for, many of which target the molecular alterations believed to contribute to the cancer’s development.
Comprehensive genomic profiling, also known as next-generation sequencing (NGS), is used to identify these molecular alterations. Duke Cancer Institute (DCI) oncologists partner with Duke University Health System (DUHS) Clinical Labs and private diagnostics companies to test patients at diagnosis and/or after the cancer grows or spreads.
While it can vary across cancer types, increasingly, targeted therapies that can save patients from needing toxic chemotherapy are becoming available at multiple points in a patient’s cancer treatment, from first line standard of care to subsequent treatment after progression on conventional therapies.
Test results are entered into a Molecular Registry of Tumors known as Frameshift MRT. This centralized informatics tool — designed, built, and coded at Duke by Michael Datto, MD, PhD, (currently the medical director of DUHS Clinical Labs and vice chair for Clinical Pathology) and Christopher Hubbard (DUHS clinical informatics architect) — helps oncologists identify if anything in their patient’s mutational profile, even extremely rare targets, can be treated with any existing targeted therapies or immunotherapies.
Duke Cancer Institute has been offering its patients NGS testing since 2014. Developing Frameshift MRT three years later to organize and optimize the growing volume and complexity of data, and the subsequent formation, in early 2018, of a weekly multidisciplinary Molecular Tumor Board to review complex patient cases was a perfectly timed great leap forward.
The Precision Cancer Medicine Initiative — launched in 2017 by DCI, the BioRepository & Precision Pathology Center (BRPC), and the Clinical Labs — was the critical push behind it.
“It had become increasingly clear that the needs of sophisticated cancer researchers were changing across all cancer types; moving away from generic, archived, cancer-tissue samples, to fresh samples, to samples with a specific molecular abnormality,” explains Shannon McCall, MD, director of the BRPC, a DCI and Duke University School of Medicine Shared Resource housed in the Department of Pathology. “This coincided with clinical advances. Providers, including at DCI, were utilizing these broad molecular profiling assays to direct the care of cancer patients. There was a need to harness all this molecular profiling data to support both cancer research and treatment. I was totally on fire to get this started. We have so many big thinkers at Duke who said, ‘Let’s think about data and what’s possible.’”
In mid-2018, Executive Director of DCI Michael Kastan, MD, PhD, a noted cancer biologist, and Chair of the Department of Pathology Jiaoti Huang, MD, PhD, a prostate cancer researcher, signed a memorandum of understanding to co-fund the staffing necessary to further support the Molecular Tumor Board — co-directed by oncologists John Strickler, MD (for solid tumor cancers), and Matthew McKinney, MD (for blood cancers) — and to manage the Frameshift MRT database. This included hiring a bioinformatician/ data analyst (Jonathan Bell, PhD) and a savvy genetics scientist (Michelle Green, PhD).
Green, fresh from a position in the molecular diagnostic testing industry, joined the Duke Pathology (with salary support from DCI) in the spring of 2019 as senior research program leader of the Molecular Tumor Board and main user and manager of Frameshift MRT. She tracks promising clinical trials and new FDA drug approvals and has configured Frameshift MRT to automatically send therapy alerts to providers when their patients' molecular profiles match any known anti-cancer drug(s). This match could include drugs that are already FDA-approved, drugs that are “emerging” with strong clinical evidence, drugs that are being tested in clinical trials, or drugs that are approved or being trialed in another cancer type.
Over the course of the COVID-19 pandemic, Green has made several significant changes to Frameshift MRT that make it more user-friendly, interactive, and accessible for clinicians and researchers, who can access the Frameshift MRT dashboard when logged into the Duke VPN. Green is available to train and advise.