Dana-Farber Cancer Institute

Not long ago, patients with metastatic melanoma had no treatment options. Today, immune checkpoint inhibitors have dramatically improved outcomes for patients with advanced melanoma. Patients have more than one option. They can try a single-agent immune checkpoint blockade or a combination of two immune checkpoint inhibitors. The combination therapy yields higher response rates but with significant added toxicity. The challenge patients and their doctors face is which option to try. There are currently no biomarkers to help physicians choose between the two. A new study led by senior author and melanoma oncologist David Liu, MD, MPH describes a machine learning-based tool that can predict which patients are likely to fare poorly with single-agent therapy and might benefit from combination therapy. The tool is not ready for clinical use but suggests the potential to develop a clinically validated tool that could help guide treatment decisions and patient outcomes. “Our unique perspective at Dana-Farber helps us see where there are opportunities to improve care for patients, and then bridge between clinical, biological, and computational science to develop tools that have the potential to help,” says Liu, who co-led the study with Dirk Schadendorf, MD, of University Hospital Würzburg in Germany. In previous research, Liu, Schadendorf, and Eliezer Van Allen, MD, chief of the Division of Population Sciences, found that a tumor’s genomic heterogeneity and low genomic ploidy predicts resistance to immune checkpoint blockade with anti-PD-1 therapy. This study builds on that research by developing a predictive machine learning model that uses genomic heterogeneity and ploidy to predict resistance to anti-PD-1 therapy. The team refined and validated the model in four cohorts including two clinical trials. The interpretable machine-learning algorithm employs a simple decision tree to robustly predict which patients are likely to resist immune checkpoint blockade with anti-PD-1 therapy. “We wanted to build a tool with high interpretability so we chose to work with simpler machine learning techniques,” says first author and computational biologist Giuseppe Tarantino, PhD. Further validation in a small group of 13 patients revealed that 43% of patients predicted to be resistant to single agent therapy responded to combination therapy, suggesting that the tool could benefit patients. The challenge, however, is that the two pieces of information required as input to the model are not standard clinical measures. The team used whole exome sequencing to determine them. A current avenue of research is to determine if these measures could be inferred using other methods that are part of standard practice. If it can be adapted to be broadly applicable in clinical practice, this tool could then be tested in prospective clinical studies to determine if it helps guide therapy choices and improves outcomes for patients with melanoma.

Exercise has long been known to promote health and wellness. But what is it actually doing inside the body? Cancer biologists Bruce Spiegelman, PhD, and Edward Chouchani, PhD, are asking this exact question in their labs. They induce exercise then capture the molecules produced during and immediately afterwards to learn what they do. "We want to understand exercise at a molecular level," says Spiegelman. "Could we use these molecules to create new therapeutics — not to replace diet and exercise but to precisely harness and amplify their effects?" Learn about the Spiegelman’s and Chouchani’s research here: https://bit.ly/40JZbQb

Meet the Community Health Outreach Team! Community Outreach Specialists partner with local organizations to provide cancer prevention education to historically marginalized populations in Greater Boston. They also partner with our expert faculty and survivors to bring cancer-specific education directly to the community. Our bilingual Community Outreach Specialists are able to present in English, Spanish, Cantonese, Mandarin, and Haitian Creole. If your organization is interested in a community education session, email dfci_communitybenefits@dfci.harvard.edu to learn more.

New research has found that rare germline genetic abnormalities could increase the risk of childhood cancers such as neuroblastoma, Ewing sarcoma, and osteosarcoma. These and other pediatric solid tumors comprise approximately one-third of all new pediatric cancer cases and are a leading cause of childhood death by disease in the US. The findings could help improve treatments or screening for these pediatric cancers. "The better we can understand the earliest events that cause these diseases, the better we’re able to think about how to improve treatment for these patients," says co-first author Riaz Gillani, MD, a pediatric oncologist at Dana-Farber/Boston Children's Cancer and Blood Disorders Center. Gillani and co-first author Ryan Collins, PhD, a computational biologist, both working in the lab of Eliezer Van Allen, MD, chief of the Division of Population Sciences, set out to take a wide look at the genomes of patients with these pediatric cancers in search of variants that could increase cancer risk. They analyzed the whole-genome sequencing of 1,766 children with cancer, 943 relatives without cancer, and 6,665 adults who were unrelated and did not have cancer. They found three important types of germline genetic variants, changes that are inherited and appear in every cell of the body from birth, that increase the risk of these pediatric cancers. The first finding was that large chromosomal abnormalities increased the risk of these three cancers four-fold in patients with XY chromosomes, children who are typically identified as males. Every cell contains 23 pairs of chromosomes, which contain the genetic instructions cells use to operate. Each chromosome has about 100 million nucleotides, the “letters” that form DNA instructions. A large chromosomal abnormality is missing about one million of these nucleotides. “That’s a really big change for DNA,” says Collins. About 80% of the abnormalities observed were inherited from the child’s parents, yet the parents did not develop cancer. This suggests that each pediatric cancer case might involve a combination of factors that could include one or more chromosomal abnormalities, other gene variants, and/or an environmental exposure. "These variants provide a bigger picture of the factors that could be involved in the development of pediatric cancers," says Gillani. While it isn’t possible today to perform the kinds of analyses this team performed on genomes in a clinical setting, it could be possible in the near-term to incorporate detection of some of these large chromosomal variants into germline genetic testing to identify more children at risk and in need of monitoring for cancer. "This work, which would not be possible without this kind of interdisciplinary collaboration and the help of our patients and their families, could inspire new approaches to early detection and intervention for these devastating cancers," says Van Allen.

Earlier this year, Susan Prieto, CMI, met with an older adult patient who was nearing the end of treatment for an incurable cancer. As a Spanish medical interpreter at Dana-Farber - Merrimack Valley, Prieto had provided essential language support to this patient many times before. During this final visit, however, the focus shifted from treatment to discussions on pain management, hospice, and spiritual care. With Nancy Nelson, BCC, a board-certified Catholic chaplain, also present, Prieto held the patient’s hand as they prayed, translating the sacred words between English and Spanish, creating a moment of comfort and connection. “The patient had a strong Catholic faith, and it was important to them that we had that goodbye. As providers, it was a privilege for Nancy and for me to be present and able to provide care,” shares Prieto. When a patient and provider speak different languages, Prieto becomes the bridge, conveying conversations with precision, empathy, and cultural sensitivity. She may assist up to 25 patients each day, facilitating clear and compassionate communication. “Being multilingual is an incredible skill, but medical interpreters go beyond that to meet professional standards,” explains Nina Scott, MHS, CMI, director of Interpreter Services. Beyond words and phrases, Prieto is attuned to the cultural nuances – gestures, idioms, and expressions – that add depth to patient-provider interactions. “Language is fluid, so I am always learning something new,” says Prieto. Moved by the dedicated care that Prieto and fellow medical interpreter Elba Salazar, CCHI Spanish, provide to patients, Nelson felt inspired to write a heartfelt prayer titled, “A Prayer for Medical Interpreters.” The prayer honors the challenging and often emotional work that medical interpreters do each day and asks for renewal of their spirits and sustainment of their multilingual skills. “During conversation and prayer, Susan’s spirituality evokes a sense of shared solidarity in offering spiritual and emotional care. With her compassion and gift for language, Susan also bridges the gap to provide spiritual support both in-person and through telehealth,” shares Nelson, who joined Dana-Farber in February. Together, Prieto and Nelson support Spanish-speaking individuals by offering spiritual care through reflective conversations and thoughtful prayers, spoken or shared on translated cards that Prieto reads aloud. Nelson hopes this experience brings a sense of spiritual peace not only to these individuals, but also to their loved ones and the staff who care for them. Prieto finds it deeply moving to be part of these spiritual care visits with Nancy, especially due to the inherent emotional element. “It can encourage reflection and enrichment of the soul,” she shares. “I’ve never worked this closely with a chaplain before, but Nancy and I have become a team. Her kindness and commitment to chaplaincy are a soothing presence that uplifts both patients and staff.”

Successful anti-cancer immune responses reported in phase 1 trial of a personalized cancer vaccine for kidney cancer. Research in Nature led by Toni Choueiri, Patrick Ott, Catherine Wu, Derin Keskin, and David Braun of Yale Cancer Center. Learn more: https://bit.ly/3CDIT3n

Dana-Farber pathologist Namrata Singh, PhD is using novel microscopy to improve cancer diagnostics and treatment. Learn more: https://bit.ly/3PSXFqb

Join Richard Stone, MD, on Feb. 27 at 6:30 p.m. for OncLive’s State of the Science Summit: Hematologic Malignancies. Topics include BTK inhibition in CLL/SLL and updates in ALL, CML, AML, and MDS. A live Q&A will follow the presentation. https://bit.ly/3Cp9gdk

We’re excited to announce that Ramesh Shivdasani, MD, PhD, has been named the inaugural incumbent of the Laurie H. Glimcher, MD, Chair at Dana-Farber. This newly endowed position was established through the collective generosity of our Institute community to honor our President and CEO Emerita, Laurie H. Glimcher, MD. Ramesh has been a pioneering researcher at Dana-Farber since 1997, an extraordinary tenure marked by innovative approaches and a steadfast commitment to advancing our fundamental understanding of cancer biology. He is a Professor of Medicine at Harvard Medical School and currently serves as Deputy Director of the Dana-Farber/Harvard Cancer Center. Until 2017, Ramesh provided care to patients, specializing in gastrointestinal cancers, and he retains the title of Distinguished Physician. Widely recognized for his leadership in gastrointestinal stem cell biology, Ramesh’s lab has laid a critical foundation for cancer prevention, intervention, and novel treatment strategies. The Laurie H. Glimcher, MD, Chair will enable Ramesh to further his groundbreaking work in understanding the biology of digestive tract cancers and stem cells. Please join us in congratulating Ramesh on this well-deserved honor and in wishing him continued success.

Two new large-scale renewable energy projects have been made possible, in part, by Dana-Farber and some familiar names from around Boston. The 200 MW Big Elm Solar project in Bell County, Texas and the 208 MW Bowman Wind project in Bowman County, North Dakota are being funded by the Consortium for Climate Solutions, a group of public and nonprofit organizations in Greater Boston with carbon reduction commitments. These projects will provide new sources of clean electricity to reduce reliance on fossil fuels and support a more resilient and diverse electricity grid. Collectively, they will generate clean power equal to the electricity use of 130,000 U.S. homes. “We know that climate change is negatively impacting our health and disproportionately affecting those in underserved populations,” says Wendy Gettleman, vice president of Facilities Management and Real Estate. “Dana-Farber is committed to doing everything we can to reduce cancer risk and improve health outcomes among communities who have been historically marginalized, and we are proud to join the Consortium to support large-scale renewable energy projects, reduce emissions, and contribute to our long-term sustainability goals,” she continues. These innovative projects are made possible by a virtual power purchasing agreement, a deal that allows companies to fund energy projects in return for carbon offsets. We partake in this agreement alongside a long list of Boston-area organizations including Harvard University, Mass General Brigham, and Massachusetts Institute of Technology. Our involvement in large-scale projects is part of its wider commitment to ecological sustainability. Several initiatives, led by our Sustainability Committee, are currently underway, including systemic changes to our supply chain, investing in energy efficient appliances and fixtures, and diverting waste. All of these efforts are connected to our fight to ease the burden of cancer. Air pollution from coal-fired power plants, for example, is a known contributor to cancer rates. Climate change caused by man-made emissions also presents challenges. Warmer and drier summers have escalated wildfires that in turn exacerbate air pollution. Natural disasters damage infrastructure and potentially cut off communities from health care resources. This instability disproportionately affects historically marginalized and underserved communities, therefore developing sustainable practices only furthers health care equity. As we continue to pursue its individual decarbonization and sustainable initiatives, our membership to the Consortium for Climate Solutions gives us a position to address the urgent need to accelerate a shift to clean energy on a larger scale where measurable impacts on electrical grid decarbonization can be realized sooner. With the Consortium’s help, the Big Elm Solar project began running in 2024 and the Bowman Wind project will be running by 2026.