Mutation Patterns That Lead to Acute Myeloid Leukemia
Using multiple methods of single-cell analysis, Dr. Ross Levine is studying how patterns of mutations in the stem cells that create blood can lead to acute myeloid leukemia. By more fully understanding how stem cells evolve and progress toward leukemia, scientists are getting closer to identifying new ways to treat and prevent cancer at precancerous stages.
Dr. Levine is Chief of the Molecular Cancer Medicine Service and Laurence Joseph Dineen Chair in Leukemia Research.
Liquid Biopsy to Monitor Diffuse Midline Glioma
Dr. Alexandra Miller is using a new diagnostic technique to more effectively treat children who have a type of brain cancer called diffuse midline glioma. In collaboration with Dr. Michael Berger, they are using liquid biopsy, a test that can detect small amounts of tumor DNA in the cerebrospinal fluid and blood, to diagnose the cancer sooner and monitor its progression. Going forward, care teams will be able to easily take multiple samples by liquid biopsy over time, so they can track changes in tumors and plan treatment accordingly.
Dr. Berger is Associate Director of the Marie-Josée and Henry R. Kravis Center for Molecular Oncology.
Cancer Risk With Bloom Syndrome
Dr. Maria Jasin is investigating a common inherited mutation in the BLM gene, which is associated with Bloom syndrome. Individuals with this syndrome have a higher chance of developing cancer of all types. Recent innovations in tumor sequencing have allowed researchers to find BLM mutations in people without Bloom syndrome. Dr. Jasin’s research aims to suggest novel therapeutic strategies that would provide hope to many people with rare and common cancers.
Dr. Jasin is William E. Snee Chair.
Outcome Disparities in Endometrial Cancer
Black women with endometrial carcinoma are more likely to die from the disease than white women, even when controlling for such factors as stage at diagnosis, obesity, and hypertension. Dr. Carol Brown is pursuing a comprehensive pathology review correlated with data from MSK-IMPACT™ to reveal whether genetic alterations in these women’s cancers can explain their disparate outcomes. The study, the largest molecular characterization of endometrial carcinomas in Black women to date, will also assess the prognostic value of genomic profiling on survival for these women.
Dr. Brown is Senior Vice President, Chief Health Equity Officer, and Nicholls-Biondi Chair for Health Equity.
Fusion-Positive Sarcomas
Fusion-positive sarcomas are aggressive cancers with distinct genetic aberrations. A team led by Dr. Neerav “Neal” Shukla is harnessing liquid biopsy, a noninvasive test, to determine how disease-defining mutations change in people undergoing treatment for these rare sarcomas. The goals: to create a standard liquid biopsy that can be used for diagnosis and to measure treatment response and tailor therapy in patients with these sarcomas.
Dr. Shukla is Director of the Pediatric Translational Medicine Program at MSK Kids, Memorial Sloan Kettering’s pediatric program.
Treatment Resistance in Renal Cell Carcinoma
One of the biggest obstacles in developing effective cancer immunotherapies is figuring out why only certain patients respond to treatment. Dr. A. Ari Hakimi is researching resistance to targeted and immune-based therapies in people with advanced renal cell carcinoma, a type of cancer that forms in small tubules of the kidneys. Dr. Hakimi and team are characterizing the role of immune cells in people who respond to or are resistant to immune and targeted therapies.
Malignant Peripheral Nerve Sheath Tumor
A malignant peripheral nerve sheath tumor (MPNST) is a highly aggressive sarcoma that cannot be easily treated with standard therapies. Dr. Ping Chi recently discovered that people with all forms of MPNST have mutations that inactivate important tumor suppressor genes. Establishing the underlying causes of MPNST has allowed Dr. Chi’s lab to identify a therapeutic strategy that counteracts these genomic mutations and simultaneously prompts the immune system to seek and destroy cancer cells.
Next-Generation CAR T Cell Therapy for Acute Myeloid Leukemia
While combining chemotherapy with the drug venetoclax (Venclexta®) has led to meaningful improvements for older people with acute myeloid leukemia, most individuals treated with this drug combination eventually see the disease progress. Dr. Anthony Daniyan is engineering a next-generation chimeric antigen receptor (CAR) T cell that targets lingering treatment-resistant cells in this rare blood cancer.
Investigating a Sarcoma Mutation
The DICER1 gene helps regulate healthy cell growth and division. When this gene is disrupted, individuals are at a greater risk of developing certain types of cancer, including sarcoma. Dr. Eric Lai and his team are researching DICER1-associated sarcomas to understand what drives cancer growth and potentially uncover new strategies to treat people with this syndrome.
Uncovering Genomic Mutations in Renal Cell Carcinoma
To improve targeted and immune-based therapies for people with a group of rare and aggressive kidney cancers called unclassified renal cell carcinoma, Dr. Yingbei Chen and collaborator Dr. Emily Cheng are studying the interaction between genomic causes of uncontrolled cancer growth and the immune system’s role in cancer progression. They hope that the findings will lead to new treatment options and better outcomes for people with this disease.