View research highlights, news and events from the Center for Cancer Research.
2022 Center for Cancer Research Annual Report
The Center for Cancer Research is the “engine for discovery” for the entire Mass General Cancer Center, stemming from the extraordinary scientists who make up our 51 faculty and 500 students, technicians and postdoctoral scientists, their deep commitment both to fundamental discovery and to its application in cancer, and an ingrained culture of collaboration between different laboratories, and between basic scientists and clinical researchers.
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2021-2022 Center for Cancer Research Seminar Series
The Center for Cancer Research Seminar Series occurs weekly and provides an opportunity for the MGH research community to learn from national and international leaders in cancer research on topics such as: cancer genetics and epigenetics, signaling and molecular therapeutics, developmental and stem cell biology, genetic model organisms, DNA damage and genomic stability, immunotherapy, hematopoiesis, lymphocyte biology and miRNA regulation, among other areas. View schedule.
Shawn Demehri, MD, PhD awarded LEO Foundation Award
Congratulations to Shawn Demehri, MD, PhD, Associate Professor of Dermatology at Massachusetts General Hospital, and a faculty member at the Center for Cancer Research at Mass General Cancer Center, for being announced as this year’s winner of the LEO Foundation Award. The award recognizes promising young talents whose work goes above and beyond to advance skin research – and Dr. Demehri receives the award for his more than noteworthy contributions to the dermatology field, his truly exciting trajectory within skin research, as well as his clinical skills. Read more.
CAR T drives acute myeloid leukemia into submission in pre-clinical studies
Mass General Cancer Center researchers have developed a novel treatment strategy that has the potential to bring the life-saving benefits of chimeric antigen receptor T-cell therapy (CAR T) to patients with acute myeloid leukemia. The method involves a combination of drug therapy to expand the number of targets on tumor cells, and an engineering approach to help the therapy adhere more tightly and durably to those targets.They describe their work in a study published in the journal Cancer Cell.
Fundamental cancer metabolism dogma revisited
A new paper in Nature Communications reveals new insights into adaptations made by cancer cells to rewire their metabolism to achieve growth and survive. Working with colon cancer tumors, Raul Mostoslavsky, MD, PhD, scientific co-director of the Mass General Cancer Center, and his team developed a fluorescent reporter that stained only a marker of glycolysis in cells of the tumor. Using this reporter and a mass spectrometry imaging approach developed by collaborator Nathalie Agar of Brigham and Women’s Hospital, the researchers found that not all cells within the colon cancer cell relied on Warburg glycolysis.
HIV drug stabilizes disease progression in metastatic colorectal cancer
New clinical research shows that lamivudine, a reverse transcriptase inhibitor widely used in HIV therapy, stopped disease progression in 25% of patients with fourth-line metastatic colorectal cancer. Findings from the trial, published in Cancer Discovery, raise the possibility of an unexpected promising direction in cancer treatment, not just colorectal cancer. The first clues to this unusual drug trial surfaced in David Ting’s lab and those of his collaborators over the past ten years.
Immunotherapy delays disease progression of high-grade meningiomas
The Center for Cancer Research's Priscilla Brastianos, MD and colleagues report in the journal Nature Communications that a class of cancer drugs known as immune checkpoint inhibitors can slow disease progression and offer hope for longer survival of patients with high-grade meningiomas.
Cancer cells that spread to different sites in the body express varying levels of targetable proteins
In a study published in Cancer Research, a team led by Shyamala Maheswaran, PhD found that, compared with primary tumors and lung and liver metastases, bone metastases overexpressed kinases that are part of the phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway, which is known to drive cancer.
Extracellular matrix proteins prevent the immune system’s natural killer cells from killing their targets in peripheral tissues
Natural killer (NK) cells are known for their innate ability to kill cancer and virus-infected cells. However, they fail to kill their targets in solid organs. In a March 2022 paper published in Science Advances, Bunting, et al. provide a novel explanation for this fundamental dilemma in the field of NK cell biology. As NK cells exit the circulation and enter organs like skin, gastrointestinal tract, pancreas, and breast, they encounter several extracellular matrix proteins like collagens that directly modulate their function from killers to helper cells. This finding could open the door to NK cell-based therapeutic interventions to improve the care of patients with cancer, infections, autoimmunity, inflammatory diseases, and transplantation.
Researchers devise sex-cell precursors with staying power
Human PGCLCs have been developed in several research centers, including the laboratory headed by Toshi Shioda, MD, PhD, in the Center for Cancer Research at Massachusetts General Hospital and Harvard Medical School. As Shioda and colleagues explain in the journal Stem Cell Reports, they have developed a method for maintaining hPGCLCs and their germ-cell-like functions in cell culture without the need for special handling, with the cells surviving and continuing to replicate for at least five months without losing their primordial germ-cell-like features.
Newly discovered DNA repair mechanisms point to potential therapy targets for cancer and neurodegenerative diseases
With co-investigators at the National Cancer Research Center in Madrid and at other centers in the U.S., Canada and China, Raul Mostoslavsky, MD, PhD and colleagues at MGH and Harvard have developed a highly sensitive method for visualizing DNA repair mechanisms at work. Using the technique, they have identified nine new proteins that are involved in DNA repair, a finding that can help researchers develop new cancer drugs, as well as methods for improving the effectiveness of existing therapies.
Cancer Center Researchers Included on Highly Cited Researchers 2021 List
We are proud to share that 28 Mass General Cancer Center researchers have been named to the Highly Cited Researchers list of 2021 by the Institute for Scientific Information at Clarivate.
This list identifies and celebrates exceptional individual researchers who are having a significant impact on the research community as evidenced by the rate at which their work is being cited by their peers. The research they have contributed is fueling the innovation, sustainability, health and security that is key for the future. Read more.
Kraft Prize Virtual Symposium - Nov 4, 2021, 1:00-5:00pm
Join us November 4th for the Jonathan Kraft Prize for Excellence in Cancer Research, presented by the Mass General Cancer Center. The 2021 Kraft Award will be presented to Aviv Regev, PhD, Head of Genentech Research and Early Development, for her groundbreaking work in cancer heterogeneity and single cell genomics.
Fibroblasts could serve as new key to enhancing personalized treatment for lung cancer patients
Three subtypes of cancer-associated fibroblasts (CAF) could guide the design of personalized treatment for lung cancer patients, according to a new study in Cancer Cell led by researchers at Massachusetts General Hospital.
“We need a new approach to characterize CAFs. Importantly, we need to gain a comprehensive understanding of different CAFs’ biological functions and their clinical significance,” says lead author Haichuan Hu, MD, PhD of the Hata lab at the Center for Cancer Research. View the press release.
Researchers identify mechanisms of resistance to drug for triple-negative breast cancer
Massachusetts General Hospital researchers, including Aditya Bardia, MD, MPH and Leif Ellisen, MD, PhD (Ellisen lab), have identified for the first time how a highly aggressive form of breast cancer can evade one of the most powerful and effective drugs used to treat it, reporting their findings in Cancer Discovery, a journal of the American Association for Cancer Research. The findings could help improve therapy and ultimately prolong survival for patients with metastatic triple-negative breast cancer. View the press release.
Researchers find immune cell “hubs” in certain tumors
Immune cells in some human colorectal tumors congregate in clusters, scientists report in Cell. The researchers, from MGH, the Broad Institute of MIT and Harvard, MIT, the Evergrande Center for Immunologic Diseases at Brigham and Women’s Hospital and Harvard Medical School, and Dana-Farber Cancer Institute say that these “hubs” might be likelier to respond to immunotherapies.
Researchers pinpoint how PARP inhibitors combat BRCA1 and BRCA2 tumor cells
In a study published in Genes and Development, a team of Mass General researchers describe how an important class of anti-cancer drugs called PARP inhibitors works, a finding that could help improve treatment and prolong survival for patients with breast cancer and other malignancies.
As Zou Lee, PhD, scientific co-director of the Mass General Cancer Center, and colleagues found, PARP inhibitors work by creating gaps in tumor-cell DNA that remain present through multiple cell cycles (the process by which cells replicate: grow, divide, repeat). They also found that BRCA1/2 mutant cancer cells cannot respond to these gaps and therefore fail to repair properly, leading to the death of tumor cells. View the press release.
The mutation-independent immunogenic effect of environmental carcinogens blocks cancer metastasis
Emerging evidence indicates that immunogenicity (i.e., improved response to immunotherapies) is a hallmark of cancers caused by exposure to environmental carcinogens. But in the past, science has focused mainly on the mutations caused by these exposures in a patient’s DNA as the reason for the immune attack. In a June 2021 paper published in Science Advances, Li et al. describe a distinct consequence of exposure to carcinogen that can have significant immunologic implications: the nongenetic induction of a chemokine called CCL21 in breast cancer cells that developed following an exposure to a chemical carcinogen. This finding could open the door to therapeutic interventions to improve the response of nonimmunogenic “cold” tumors to current cancer immunotherapies. View the press release.
More news from the Demehri lab:
- Common moles could serve as players in battling melanoma and preventing its recurrence
- New Insights on How Inflammatory Molecule Contributes to Skin and Pancreatic Cancers
Mass General Cancer Center to Host Inaugural Arthur and Sandra Irving Cancer Immunology Symposium, March 22-24
The Mass General Cancer Center will host the Arthur and Sandra Irving Cancer Immunology Symposium from March 22-24, 2021, virtually bringing together 14 accomplished faculty mentors who will discuss their research, discoveries, and distinguished careers in cancer immunology with 44 talented young scientists and physicians from around the world. Learn more.
Cosmetic laser may boost effectiveness of certain anti-cancer therapies
Use of a cosmetic laser invented at Massachusetts General Hospital may improve the effectiveness of certain anti-tumor therapies and extend their use to more diverse forms of cancer. The strategy was tested and validated in mice, as described in a study published in Science Translational Medicine.
In an attempt to expand the benefits of immune checkpoint inhibitors for additional patients, a team led by CCR faculty member David E. Fisher, MD, PhD, director of the Mass General Cancer Center’s Melanoma Program and director of MGH’s Cutaneous Biology Research Center, conducted experiments in mice with a poorly immunogenic melanoma that is not hindered by immune checkpoint inhibitors. The researchers found that exposing the melanoma cells to ultraviolet radiation caused them to take on more mutations, which made immune checkpoint inhibitors more effective at boosting the immune response against the melanomas. View the press release.
More news from the Fisher lab:
Study uncovers two phases of infection in patients with severe COVID-19 pneumonia
New research led by investigators at Massachusetts General Hospital and published in Nature Communications provides insights that could help improve treatment strategies for infected patients.
To analyze SARS-CoV-2 at the tissue level, the scientists examined autopsied material from 24 patients who succumbed to COVID-19. “We used a method called RNA in situ hybridization to visualize the actual SARS-CoV-2 virus in human lung specimens. This assay is now a clinical test being used at MGH to understand what tissues can be infected by the virus,” explains co-author David T. Ting, MD, associate clinical director for Innovation at the Mass General Cancer Center and an assistant professor of Medicine at Harvard Medical School. View the press release.
CCR Investigators Named Bits to Bytes Program Awardees
Congratulations to CCR faculty Raul Mostoslavsky, MD, PhD, Nabeel Bardeesy, PhD, Gad Getz, PhD, and Leif Ellisen, MD, PhD, who along with Keith Flaherty, MD have been awarded Bits to Bytes program funding from the Massachusetts Life Sciences Center (MLSC) for their project "An Integrative Platform to Understand and Exploit Cancer Metabolism."
MLSC launched Bits to Bytes in 2019 to provide grants for projects that generate and analyze large datasets to answer pressing life science questions, and to attract and train data scientists in the Commonwealth. View the press release.
Lee Zou, PhD and Raul Mostoslavsky, MD, PhD Named Scientific co-Directors
After nine years as the Scientific Director of the Mass General Cancer Center and Center for Cancer Research, Dr. Nick Dyson is stepping down from his role. Succeeding him are Lee Zou, PhD and Raul Mostoslavsky, MD, PhD, who will serve as Scientific co-Directors. Both of these highly accomplished researchers are ready to ensure that Mass General Cancer Center continues on its outstanding trajectory of discovery and innovation in cancer research. Read more.
Ultrahigh-throughput magnetic sorting of large blood volumes for epitope-agnostic isolation of circulating tumor cells
A team at Massachusetts General Hospital has devised a new ultrahigh-throughput microfluidic chip (the LPCTC-iCHIP) that improves sensitivity of CTC-based assays 100-fold as compared to the existing approaches. The team’s paper appeared recently in the May 2020 issue of Proceedings of the National Academy of Sciences.
“Drs. Mehmet Toner, Daniel Haber, and Shyamala Maheswaran applied the precision of microfluidics to rare cell sorting and helped establish the field of liquid biopsy research about ten years ago,” says Avanish Mishra, PhD, a research fellow at the Mass General Cancer Center and Harvard Medical School, who was the co-lead author on the LPCTC-iCHIP project along with Taronish Dubash, PhD. “With this novel new technology and our unique process using the leukopak, we transform CTC screening from a 10 mL blood sample to whole human blood; hoping to bring highly reliable liquid biopsies into the clinic.” View the press release.
Genomic characterization of human brain metastases identifies drivers of metastatic lung adenocarcinoma
Cancer researchers at Massachusetts General Hospital and affiliated institutions have identified changes in lung cancer-promoting genes that may allow the disease to metastasize to the brain. Their work, which points to possible therapies for preventing or treating brain metastases from lung cancer, is described in the March 2020 issue of Nature Genetics.
“It’s a terrible complication of lung cancer, because it’s associated with significant mortality, and the median survival in this patient population is on the order of months. Unfortunately, the treatment options are limited and there is no established standard of care for most patients with brain metastases from lung adenocarcinoma,” said principal investigator Priscilla K. Brastianos, MD, from the Mass General Cancer Center. View the press release.
Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis
Hormone receptor-positive breast cancer can spread throughout the body via the bloodstream as circulating tumor cells, or CTCs, which eventually reach distal (remote) body sites to form metastatic tumors. An increase in ribosomes, the protein-making machinery found in every living cell, increases their potential to form metastasis, report investigators from Massachusetts General Hospital Cancer Center and Harvard Medical School. The findings were published in a March 2020 issue of Science.
“The Haber/Maheswaran lab has been one of the pioneers in being able to isolate, analyze and now use CTCs that are derived from patient blood samples. They offer many advantages and opportunities for understanding the metastatic pathways that are involved in advanced breast cancer,” says investigator Douglas S. Micalizzi, MD, PhD, from the MGH Cancer Center. View the press release.
Tumor sequencing has traditionally focused on protein-coding genes, yet these only comprise roughly one percent of the human genome. The remainder contains important regulatory sequences that tightly control gene expression and production of proteins, making sure genes are turned on at the right time in the correct cells.
The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium, a joint effort of over 1,300 researchers from 37 countries, published a comprehensive in-depth analysis of more than 2,600 primary tumor genomes in the Feb 2020 issue of Nature. As part of this effort, CCR faculty members Gad Getz and Esther Rheinbay, together with their colleagues, studied the landscape of protein-coding and non-coding regulatory driver events in cancer. Their study presents a novel strategy to analyze recurrent driver events in whole cancer genomes, and shows that although there are clear drivers in non-coding regions, the majority of driver genetic changes alter proteins. This work also highlights that there are still challenges in finding genetic drivers of cancer and that we will need to sequence many more tumors to fully map and understand the genetic causes underlying each individual patient’s disease. View the press release.
TATR protects the genome by sensing R loops
R loops are transcription intermediates that contain DNA:RNA hybrids. In cancer cells, R loops often accumulate at aberrantly high levels, leading to genomic instability and DNA damage. In a February 2020 paper published in Molecular Cell, Matos and colleagues in the Zou laboratory reported that the ATR kinase is a key sensor of R loops and a suppressor of R loop-associated DNA damage. This paper reveals the molecular mechanisms by which human cells, especially cancer cells, use ATR to cope with R loops in their genomes, suggesting that inhibition of ATR may be an effective strategy to selectively kill cancer cells harboring high levels of R loops.
2020 Research Highlights
- Large-Scale Topological Changes Restrain Malignant Progression in Colorectal Cancer
- Temporal and spatial heterogeneity of host response to SARS-CoV-2 pulmonary infection
- Ultrahigh-throughput magnetic sorting of large blood volumes for epitope-agnostic isolation of circulating tumor cells
- Genomic characterization of human brain metastases identifies drivers of metastatic lung adenocarcinoma
- Analyses of non-coding somatic drivers in 2,658 cancer whole genomes
- Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis
- ATR Protects the Genome against R Loops through a MUS81-Triggered Feedback Loop
Publications By Our Researchers