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Dan G. Duda, DMD, Ph.D.

AIMBE College of Fellows Class of 2020
For outstanding contributions to understanding the metastatic process in cancer and combating treatment resistance in hepato-biliary and pancreatic malignancies.

Sequencing of drug combinations could amplify the anti-tumor immune response in liver cancer

Via Mass General Hospital | March 15, 2022

A new therapeutic strategy for hepatocellular cancer (HCC) that initially primes the tumor with an immune checkpoint inhibitor before using a multikinase inhibitor drug showed great promise for treating patients with the deadly disease, a Massachusetts General Hospital (MGH) study found. In a paper published in Journal of the National Cancer Institute, researchers reported that the new sequencing approach enhanced the effectiveness of the dual drug therapy, potentially allowing de-escalation of the prolonged use of medications and thus reducing toxic drug exposure.

“A regimen of a multikinase inhibitor followed by immune checkpoint blockade, alone or in combination, has historically been the way to test new treatment approaches in HCC patients,” says Dan G. Duda, DMD, PhD, director of translational research in GI Radiation Oncology at MGH and senior author of the study. “No one knew, however, what the effect might be of reversing the sequence of these therapies… Continue reading.

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Researchers restore function in a gene that can suppress liver cancer and enhance immunotherapy

Via Massachusetts General Hospital | February 9, 2022

A team of researchers from Massachusetts General Hospital (MGH) and Brigham and Women’s Hospital (BWH) has reprogrammed the tumor microenvironment of liver cancer by using mRNA nanoparticles. This technology, similar to the one used in COVID-19 vaccines, restored the function of the p53 master regulator gene, a tumor suppressor mutated in not just liver but also other types of cancer. When used in combination with immune checkpoint blockade (ICB), the p53 mRNA nanoparticle approach not only induced suppression of tumor growth but also significantly increased antitumor immune responses in hepatocellular carcinoma (HCC) laboratory models. The results of the study were published in Nature Communications.

“The reprogramming of the cellular and molecular components of the tumor microenvironment could be a transformative approach for treating HCC and other cancers,” says co-senior author Jinjun Shi, PhD, with the Center for Nanomedicine at BWH, who developed the platform with MGH liver cancer biologist and co-senior author Dan G. Duda, DMD, PhD. “By using this new approach, we’re targeting specific pathways in tumor cells with mRNA nanoparticles. These tiny particles provide the cells with the instructions to build proteins, which, in the case of HCC, delayed tumor growth and rendered the tumor more responsive to treatment with immunotherapy… Continue reading.

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Dan Duda Elected to 2021 AAAS Fellows

Via Harvard Medical School | January 26, 2022

Three Harvard Medical School researchers have been elected by their peers as 2021 Fellows of the American Association for the Advancement of Science (AAAS) for their contributions to medical sciences. They are among the 564 scientists, engineers, and innovators from 24 scientific disciplines being recognized for their scientifically and socially distinguished achievements.

Dan Duda, HMS associate professor of radiation oncology at Massachusetts General Hospital, was recognized for using medical and biological research tools to reveal new mechanisms that underlie cancer treatment resistance and for new ways to improve therapy, particularly using liver cancer models… Continue reading.

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Discovery of a new approach to inhibiting a highly treatment-refractory liver cancer

Via EurekAlert | January 12, 2021

Reprogramming the rich connective tissue microenvironment of a liver cancer known as intrahepatic cholangiocarcinoma (ICC) inhibits its progression and resistance to standard chemotherapy in animal models, researchers from Massachusetts General Hospital (MGH) have found. This new treatment for a disease with extremely poor outcomes uses antibodies to block placental growth factor (PlGF), a member of the vascular endothelial growth factor (VEGF) family, which has been widely studied for its role in new vessel formation in cancers. PlGF is highly expressed in ICC compared to normal liver tissue, and blocking it reduces the production of connective tissue while increasing the efficacy of chemotherapy and survival in mice with ICC. These findings were reported in Gut, the journal of the British Society of Gastroenterology.

“We were able to demonstrate that PlGF is a mediator of ICC progression, and that antibody blockade of PlGF in ICC models inhibited the activity of cancer-associated fibroblasts (CAFs), which produce connective tissue and also provide ICC cells with pro-survival and pro-invasion signals,” says Dan G. Duda, DMD, PhD, director of Translational Research in GI Radiation Oncology at MGH, and senior author of the study. “Our findings suggest that PlGF inhibition is a potential therapeutic target that could have implications for other emerging combination therapies that have shown promise against ICC, a largely intractable disease with a dismal prognosis… Continue reading.

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Combination therapy might improve outcomes in treatment-resistant liver cancer

Via Massachusetts General Hospital | November 30, 2020

A combination cancer therapy that is effective against treatment-resistant hepatocellular carcinoma (HCC) by inhibiting tumor growth and increasing survival has been identified by researchers at Massachusetts General Hospital (MGH). In a paper published in the Journal for ImmunoTherapy of Cancer, the investigators describe how the dual therapy — which combines the multikinase inhibitor drug regorafenib to “reprogram” the tumor immune microenvironment, and programmed cell death 1 (PD1) antibodies to stimulate anti-tumor immunity — improved survival in mouse models of HCC beyond what each therapy could have achieved alone.

“The holy grail of immunotherapy in treating solid cancers like HCC is to draw cancer-fighting T-cells inside the tumor,” explains Dan G. Duda, DMD, PhD, director of translational research in GI Radiation Oncology at MGH and senior author of the study. “We found that regorafenib delivered at the right intermediate dose tricks cancer cells into expressing a chemokine known as CXCL10 which, in turn, triggers intratumoral T-cell infiltration… Continue reading.

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Dr. Dan Duda Inducted into AIMBE College of Fellows

Via AIMBE | March 30, 2020

WASHINGTON, D.C. — The American Institute for Medical and Biological Engineering (AIMBE) has announced the induction of Dan G. Duda, DMD, Ph.D., Director of Translational Research in GI Radiation Oncology, Department of Radiation Oncology, Massachusetts General Hospital, Investigator, Edwin L. Steele Laboratories for Tumor Biology, Massachusetts General Hospital Research Institute, Associate Professor of Tumor Biology, Harvard Medical School, to its College of Fellows.

Election to the AIMBE College of Fellows is among the highest professional distinctions accorded to a medical and biological engineer. The College of Fellows is comprised of the top two percent of medical and biological engineers. College membership honors those who have made outstanding contributions to “engineering and medicine research, practice, or education” and to “the pioneering of new and developing fields of technology, making major advancements in traditional fields of medical and biological engineering, or developing/implementing innovative approaches to bioengineering education.”

Dr. Duda was nominated, reviewed, and elected by peers and members of the College of Fellows for “outstanding contributions to understanding the metastatic process in cancer and combating treatment resistance in hepato-biliary and pancreatic malignancies.

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