Researchers at MSK made discoveries about cancer at its most fundamental levels, increasing understanding of the disease and opening the possibility of new therapies.
Researchers at Memorial Sloan Kettering Cancer Center (MSK) continued to make meaningful strides against cancer in 2022. Laboratory studies conducted at the Sloan Kettering Institute (SKI) and across the institution contributed to the global understanding of how cancer arises, grows, and spreads — opening new possibilities for future therapies and treatments.
“To understand a complex disease like cancer, with its many types and forms, you have to investigate it at its most fundamental levels. This work spans fields including genetics, immunology, molecular biology, pharmacology, and many more,” says MSK President and CEO Selwyn M. Vickers, MD, FACS. “What I want everyone to understand is that MSK is as passionate about our research enterprise as we are about providing unparalleled patient care.”
MSK is home to more than 120 research laboratories focused on better understanding every type of cancer. This includes more than 100 labs at SKI, a dedicated experimental research arm within the larger cancer center. MSK scientists are global leaders in the field, publishing their work frequently in leading scientific and medical journals, and presenting it at top national and international conferences.
Here are some of the most exciting discoveries reported over the past year, in chronological order:
A New Type of Immunotherapy Targets Elusive Cancer Cells
Some people don’t respond to cancer treatment using chimeric antigen receptor (CAR) T cells because their cancer cells have very low levels of the targeted protein, or antigen. A team led by SKI physician-scientist Michel Sadelain, MD, PhD, developed a way to engineer highly sensitive T cells that can destroy cancer cells with low antigen levels. These redesigned T cells, called HLA-independent T cell receptor (HIT) T cells, could be effective when conventional CAR T therapies would fail. The team reported this advance in Nature Medicine on January 13, 2022.
Deep Dive Into Genetic Data Yields Metastasis Clues
Can a tumor’s DNA mutations predict whether and when the cancer will spread? A research team led by MSK computational oncologists Francisco Sanchez-Vega, PhD, and Nikolaus Schultz, PhD, analyzed genomic data from 25,000 patients with 50 different types of cancer to find out. The answer, reported February 3, 2022, in Cell, was “No”; however, the six-year investigation provides important new clues about cancer’s ability to metastasize.
A New Twist on an 80-Year-Old Biochemical Pathway
A team of SKI scientists led by cell biologist Lydia Finley, PhD, reported discovering a previously unappreciated metabolic pathway — an alternate version of the famous Krebs/tricarboxylic acid (TCA) cycle. This new version of the TCA cycle allows cells to use the carbons in nutrients to build new cell biomass rather than burn them for energy. The findings, which were reported on March 9, 2022, in Nature, have broad implications for understanding how cells adapt their metabolism to meet changing needs.
Scientists Find Potential New ‘Soldier’ for Cancer Immunotherapy
A team led by SKI immunologist Ming Li, PhD, discovered a new immune cell type that might be weaponized for immunotherapy. The new cells, which the scientists call innate-like T cells, differ in notable ways from the conventional target of many immunotherapies — the cytotoxic (aka “killer”) T cells. The discovery, reported in the April 20, 2022, issue of Nature, raises hopes of narrowing the gap between people who respond to immunotherapy and those who do not.
A Sensor Sniffs for Cancer, Using Artificial Intelligence
MSK researchers, led by Kravis WiSE postdoctoral fellow Mijin Kim, PhD, and SKI biomedical engineer Daniel Heller, PhD, developed an AI-assisted nanosensor that can detect ovarian cancer signals in the blood. Once validated, the test could potentially aid early detection of ovarian cancer, which is urgently needed. The scientists reported the research in the May 12, 2022, issue of Nature Biomedical Engineering.
Finding a New — and Common — Subtype of Prostate Cancer
Scientists at MSK and Weill Cornell Cancer Center identified a previously uncharacterized subtype of hormone-resistant prostate cancer that accounts for about 30% of all cases. The finding, reported in Science on May 27, 2022, could pave the way for targeted therapies for people with this subtype of prostate cancer. The team, led by MSK physician-scientist Yu Chen MD, PhD, a member of the Human Oncology and Pathogenesis Program, used organoids and patient-derived xenografts (cells from tumors implanted into immunodeficient mice) to identify the subtype, which they call stem cell-like (SCL), because some of the genes that are turned on in the cells are reminiscent of those in stem cells.
A Natural Defense Against Viruses Can Lead to Cancer Cell Mutations
APOBEC3 enzymes normally play a role in defending the body from viruses by disrupting their DNA. A research team led by SKI molecular biologist John Maciejowski, PhD, found strong evidence that the enzymes also play a role in causing cancer-related mutations. The discovery was reported in Nature on July 20, 2022.
A Surprising Way for Pancreatic Cancer to Spread
Schwann cells wrap around nerves like insulation around an electric cable. The laboratory of MSK physician-scientist Richard J. Wong, MD, FACS, discovered that Schwann cells organize into tracks, through which pancreatic cancer cells can travel. In addition to blood vessels and the lymphatic system, the Schwann cells represent a third avenue for cancer to spread from the pancreas. As the researchers reported in the August 3, 2022, issue of Cancer Discovery, a protein called c-Jun is key to this process.
SKI Scientists Solve 30-Year-Old Mystery About p53 Protein — Dubbed ‘Guardian of the Genome’
More than half of all cancers have mutations in a gene called p53, often called the “guardian of the genome.” Cells without working p53 are unable to properly repair damaged DNA, leading to a buildup of mutations. A study led by SKI cancer biologist Scott Lowe, PhD, found that loss of p53 is followed by an orderly progression of predictable genetic changes — not genetic chaos, as previously believed. The researchers, who reported this finding in the August 17, 2022, issue of Nature, say that knowing that there are “rules” to the genetic evolution of tumors suggests a different way of thinking about treating them.
MSK Researchers Discover How Cancer Cells Change Identity To Escape Therapies
Some prostate tumor cells completely change their identity to resist drugs. This transformation, known as lineage plasticity, allows cancer cells to convert to a different cell type. Research done in laboratory models and led by physician-scientist Charles Sawyers, MD, and Sloan Kettering Institute computational biologist Dana Pe’er, PhD, identified signaling pathways that, if blocked, resensitize cells to therapy — potentially opening the door to new clinical approaches. The findings are reported in the September 2, 2022, issue of Science.
New MACHETE Technique Slices Into Cancer Genome To Study Copy Number Alterations
MACHETE, a new CRISPR-based technique to study large-scale genetic deletions efficiently in laboratory models, shed new light on a genetic change that contributes to about 15% of all cancers. The finding, reported on December 7, 2022, in Nature Cancer by postdoctoral fellows Kaloyan Tsanov, PhD, and Francisco “Pancho” Barriga, PhD, in the laboratory of SKI cancer biologist Scott Lowe, PhD, might help identify patients likely to respond to immunotherapies.
Shedding Light on Ovarian Cancer Resistance to Immunotherapy
Ovarian cancers have been stubbornly resistant to immunotherapy compared with many other cancers. A study led by computational oncologist Sohrab Shah, PhD, and medical oncologist Dmitriy Zamarin, MD, PhD, found that ovarian cancer is even more complex than previously understood. The teams discovered there are profound differences among tumors of the same high-grade serous subtype and between the different tumor sites within the same patient. They also learned that ovarian tumors develop new mutations to hide from the immune system as they spread. The research, reported on December 14, 2022, in Nature, reveals mechanisms driving resistance, providing an opportunity to find better ways to improve treatments.
