Advances at Mass General Cancer Center

Advances at Mass General Cancer Center is our electronic publication that highlights our investigators’ recent publications in high-profile journals.

Current Article

Prion-Like Domains Drive Tumor Growth in Ewing Sarcoma

What role does the EWSFLI1 fusion protein play in activation in Ewing sarcoma?
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Contributor

  • Miguel N. Rivera, MD

    Assistant Professor of Pathology, Mass General Hospital and Harvard Medical School; Investigator, Center for Cancer Research, Mass General Cancer Center

Unlike adult cancers, pediatric cancers tend to feature few genetic mutations, and these mutations most often affect genes that play a role in gene expression and regulation. Ewing sarcoma is one such form of pediatric cancer. It grows aggressively, metastasizes frequently, and is driven by a single genetic defect: a fusion between the genes EWS and FLI1. How the EWS-FLI1 fusion protein promotes tumor formation is not fully understood and is the focus of new research from the lab of Miguel N. Rivera, MD, Assistant Professor of Pathology at Massachusetts General Hospital and Harvard Medical School, and an Investigator at the Center for Cancer Research at Mass General Cancer Center.

While the FLI1 is a well-known DNA-binding transcription factor involved in controlling gene expression, the function of EWS is less well defined. One prominent feature of EWS is that it contains prion-like domains that make it prone to pathological aggregation in neurodegenerative disease. In research published in Cell in September 2017, Dr. Rivera and his team showed that these prion-like domains, which are maintained by EWS-FLI1 fusion proteins, are instrumental in activating Ewing sarcoma oncogenes. Continue Reading

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This podcast is a companion to Mass General Cancer Center’s electronic publication, and both are centered around our investigators' recent publications in high-profile journals. Each expert will give you insight into who they are and what inspires them to do what they do every day. A deeper dive into their research will better your understanding of where our experts’ ideas come from, where they will go from here, and what the future has in store in their particular field of research.

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2018 and 2017 Past Articles

March 2018
February 2018
January 2018
December 2017
November 2017
October 2017
September 2017
August 2017
July 2017
June 2017

March 2018

Beating Resistance to Immunotherapy in Metastatic Melanoma

Can defects in the B2M gene that drive resistance be overcome by epigenetic or natural killer cell therapies? Download this article

Contributor

  • Nir Hacohen, PhD

    Director, Center for Cancer Immunology, Mass General Cancer Center;
    Professor of Medicine, Harvard Medical School;
    David P. Ryan, MD, Endowed Chair in Cancer Research, Funded
    by a Gift from Arthur, Sandra, and Sarah Irving

Immune checkpoint blockade (CPB) therapy has a high success rate at killing metastatic melanoma compared with other therapies. CPB therapy works by stimulating the body’s T-cells to identify and destroy tumor cells that present cancer-specific antigens. But resistance to CPB—both primary and acquired—remains a major cause of mortality. Continue Reading


February 2018

New Genetic-Based Treatment for Glioneuronal Tumors

Can identifying oncogene fusions that are susceptible to treatment help with reducing these tumors? Download this article

Contributor

Glioneuronal tumors are a rare group of uncommon, diverse primary central nervous system tumors with few treatment options aside from surgical resection. Radiation is offered if the tumor is not totally resected or if it displays high-grade aggressive behavioral features or recurrence. Historically, the molecular understanding of these tumors has been quite limited, confounding the ability to treat them with targeted therapy. Continue Reading


January 2018

New Combination Therapy for Renal Cell Carcinoma

Can understanding glutamine’s role in renal cancer cell metabolism lead to successful treatments for renal and other cancers? Download this article

Contributor

  • Othon Iliopoulos, MD

    Clinical Director, von Hippel-Lindau Disease/Familial Renal Cell Cancer, Massachusetts General Hospital Cancer Center; Associate Professor of Medicine, Harvard Medical School

Cancer cell metabolism has only recently become a major subject of study for cancer researchers hunting for cures. Hypoxia, or a shortage of oxygen, is a hallmark of human cancer cells. But because oxygen is critical to cell growth, cancer cells tend to adapt by reprogramming cell metabolism. In particular, researchers have recently learned that these cells rely on amino acid glutamine instead of glucose to metabolize carbon. Continue Reading


December 2017

Secondary FGFR2 Mutations Drive Drug Resistance to FGFR Inhibitors in Bile Duct Cancer

Can understanding the genetic mechanisms driving resistance to the FGFR inhibitor BGJ398 lead to better therapies for bile duct and other cancers? Download this article

Contributor

  • Lipika Goyal, MD, MPhil

    Medical Oncologist, Tucker Gosnell Center for Gastrointestinal Cancers, Mass General Cancer Center; Instructor in Medicine, Harvard Medical School

Intrahepatic cholangiocarcinoma (ICC) is a rare cancer of the bile ducts in the liver, with limited treatment options and a poor prognosis. In its advanced stages, only one chemotherapy regimen has been shown to improve survival, but those treated usually don’t live more than a year. In 2013, however, researchers at the University of Michigan discovered that a specific kind of genetic alteration in the fibroblast growth factor receptor (FGFR) pathway recurs in patients with bile duct cancer. These so-called FGFR2 “fusions” were subsequently found to have an incidence of about 10% to 20% in ICC—and are now promising therapeutic targets in this disease. Continue Reading


November 2017

Identifying Therapeutic Targets for IDH-Mutant Brain Tumors

Can single-cell RNA sequencing of IDH-mutant glioma samples help identify cell lineages, phenotypes and microenvironments that would respond to specific therapies? Download this article

Contributor

  • Mario Suvà, MD, PhD

    Associate Professor of Pathology, Mass General Cancer Center and Harvard Medical School

The heterogeneity between tumors and within a tumor can contribute to the failure of therapy and lead to the progression of cancer. Many factors play a role in this heterogeneity: Cancer cells within a tumor have differences in genotypes and phenotypes, and tumors differ in the composition of their microenvironments. While the genetic signatures of tumors are now fairly easy to discern with the common strategy of bulk genomic analysis of samples collected from large cohorts, phenotypes and microenvironments are harder to characterize in this manner. Bulk tissue profiles tend to average the diverse cell types within each tumor, masking critical differences in phenotype expression and microenvironments. Continue Reading


October 2017

Epigenetic-Metabolic Pathways in Pancreatic Tumor Cells

Can understanding metabolic reprogramming of genetic material in some cancer cells lead to new treatments? Download this article

Contributor

  • Nabeel Bardeesy, PhD

    Associate Professor of Medicine, Mass General Cancer Center and Harvard Medical School

A mutation in the KRAS gene, which plays a role in regulating cell division and survival, is commonly found in human cancers, such as pancreatic and non-small cell lung cancers. While KRAS has been shown to be important in the sustained growth of these tumors, effective KRAS inhibitors have been elusive, and these tumor types remain very difficult to treat. Some researchers propose that effective treatment for such cancers may rely on identifying therapeutic vulnerabilities that result from other mutations the patients might also carry. Continue Reading


September 2017

Dynamic HER2 Switch Discovered in Circulating Breast Cancer Cells

Can understanding plasticity of HER2 protein states in breast cancer cells of treatment-resistant tumors lead to better treatments? Download this article

Contributors

  • Shyamala Maheswaran, PhD

    Associate Professor of Surgery, Mass General Cancer Center and Harvard Medical School

  • Aditya Bardia, MD, MPH

    Medical Oncologist, Mass General Cancer Center; Assistant Professor of Medicine, Harvard Medical School

Researchers Shyamala Maheswaran, PhD, Aditya Bardia, MD, and Nicole Vincent Jordan, PhD, of Massachusetts General Hospital Cancer Center, along with Daniel Haber, MD, PhD, director of Mass General Cancer Center, using ex vivo cultures of circulating tumor cells derived from breast cancer patients, have shown that breast cancer cells can spontaneously switch from a HER2-negative to a HER2-positive state and vice versa. These two populations have different molecular pathways that drive their growth. Several growth-factor-driven pathways are active in the HER2-positive cells, and one pathway, called Notch, is active in the HER2-negative cells. Continue Reading


August 2017

Improved Outcomes and Palliative Care

Can palliative care help patients with hematologic malignancies? Download this article

Contributor

  • Areej El-Jawahri, MD

    Program Director, Bone Marrow Transplant Survivorship, Mass General Cancer Center; Assistant Professor of Medicine, Harvard Medical School

Palliative care, which aims to alleviate symptoms and improve mood for patients with life-threatening illnesses, is increasingly common for individuals with solid tumors in advanced stages. But such care is rarely prescribed for patients with hematologic malignancies, even though standard hematopoietic cell transplantation (HCT) treatment for such cancers requires some of the highest dose chemotherapy—a course that can result in high symptom burdens and long, taxing hospital stays. Continue Reading


July 2017

Antitumor Immunity and Its Evasion by Tumors

How do tumors evolve to evade the immune response? Download this article

Contributors

  • Nir Hacohen, PhD

    Director, Cancer Immunotherapy at Mass General Cancer Center; Associate Professor of Medicine, Harvard Medical School & Broad Institute

  • Gad Getz, PhD

    Director, Bioinformatics, Mass General Cancer Center and Department of Pathology; Paul C. Zamecnik Chair in Oncology, Mass General Cancer Center; Director, Cancer Genome Computational Analysis, Broad Institute Member, Broad Institute Associate Professor of Pathology, Harvard Medical School

While some patients with cancer mount a strong immune response against their tumors, most have no significant immune response against these invaders. Little is known, however, about what genetic and environmental factors shape an individual tumor’s response to the immune system, or about how the tumor and the immune system interact at a cellular and molecular level. Continue Reading


June 2017

A New Therapeutic Target for Pancreatic Cancer

Can better understanding an epigenetic pathway lead to clues in one of the most lethal cancers? Download this article

Contributor

  • Raul Mostoslavsky, MD, PhD

    Principal Investigator, Mostoslavsky Laboratory, and Kristine and Bob Higgins Mass General Hospital Research Scholar, Mass General Hospital Cancer Center; Associate Professor of Medicine, Harvard Medical School

Pancreatic ductal adenocarcinoma (PDAC) accounts for 90% of all pancreatic cancers, and is one of the most lethal cancers in humans. PDAC is characterized by mutant KRAS, a gene involved in regulating cell division, but little is known about the molecular processes governing initiation, progression and metastasis in PDAC. As a consequence, no good new therapeutic targets have been identified for the cancer in three decades. Despite active research in this field, standard chemotherapy remains the primary treatment available for PDAC, and survival rates are under 5% after a year. Continue Reading

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