In 2026, the Human Oncology and Pathogenesis Program (HOPP) celebrates 20 years of discovery, leadership, and impact in translational oncology. HOPP supports innovation and collaboration between talented physicians and scientists who are at the leading edge of bench- to-bedside research.
Featured Stories
HOPP was created to bridge clinical and laboratory worlds and accelerate translational cancer research - bringing targeted therapies to patients sooner. Over 20 years, HOPP has grown into a hub for ideas and collaboration at MSK. HOPP investigators are embedded in both disease management teams and laboratories, connecting researchers and resources across disciplines, and putting HOPP at the heart of many of the new and emerging precision therapies developed at MSK.
Prostate Cancer: The Androgen Receptor and Beyond
Charles Sawyers is a pioneer in precision oncology, co-developing imatinib and dasatinib for the treatment of chronic myeloid leukemia. Recruited as inaugural Chair of HOPP in 2006, his attention had turned to a new problem: understanding why prostate cancers stop responding to treatment. Studies from his team and other HOPP and MSK labs are behind multiple key discoveries in prostate cancer modeling, biology, and precision medicine that have changed clinical practice.
Sawyers and team discovered that overactive androgen receptor (AR) signaling could drive resistance to therapy, leading them to develop the AR inhibitors enzalutamide and apalutamide. Early (Phase I/II) trials of the targeted antiandrogen therapy (apalutamide/Erleada) showed lowered circulating prostate specific antigen (PSA), suggesting that prostate tumors had stopped growing.
Drug Shows Activity in Men with Advanced Prostate Cancer
A new multi-center study shows that an experimental drug lowers prostate specific antigen (PSA) levels - a marker for tumor growth - in men with advanced prostate cancer for whom traditional treatment options have failed.
Sawyers and surgeon, Dr. Brett Carver discover that androgen receptor signals cross-talks with the PI3K pathway, a signal that drives many other forms cancer. This work suggests Inhibiting both signaling pathways (using AR- and PTEN-inhibitors) as a strategy to treat antiandrogen resistance.
Memorial Sloan Kettering Researchers Discover How Prostate Cancer Disease Pathways Regulate Each Other
Memorial Sloan Kettering researchers have discovered that the AR and PI3K disease pathways regulate each other through reciprocal negative feedback.
Phase 3 clinical trial results show that enzalutamatide significantly improved overall survival in patients with advanced prostate cancer. Enzalutamide is targeted specifically to bind to androgen receptors in cancer cells, inhibiting the ability of the receptor to drive cancer growth.
Targeted Therapy Improves Overall Survival in Men with Late-Stage Prostate Cancer
The investigational oral drug MDV3100 significantly improved overall survival in patients with advanced prostate cancer, results of a large, phase III study show.
Dr. Sawyers and Dr. Arul Chinnaiyan from the University of Michigan lead the prestigious Stand Up to Cancer (SU2C)-Prostate Cancer Foundation Prostate Dream Team: Precision Therapy of Advanced Prostate Cancer alongside. They coordinate an international team that will develop precision medicine for metastatic prostate cancer, matching treatment to specific tumor characteristics.
Dr. Yu Chen publishes his work on prostate cancer organoids. Organoids are a transformative research tool that allow investigators to use patient-derived tumor models to understand tumor biology and rapidly test therapeutic strategies before moving into more difficult-to-make genetic models or clinical trials.
The Newest Precision Medicine Tool: Prostate Cancer Organoids
Research led by investigators at Memorial Sloan Kettering has shown for the first time that organoids derived from human prostate cancer tumors can be grown in the laboratory.
Prostate Cancer Organoids Provide New Tool for Evaluating Therapies
Researchers have created tiny structures called organoids from patients’ prostate tumors. These organoids will allow the study of tumors in greater detail and enable correlation of genetic mutations with drug response.
Pairing genomic data with sophisticated molecular tools and patient-derived tumor models, the Sawyers lab revealed how prostate cancer cells can evade treatment by acquiring attributes of stem cells. Sawyers and collaborators continue to describe how prostate cancers co-opt cell pathways to evade treatment at the molecular and genetic level.
New Discovery Explains How the Prostate Gland Regenerates Itself
Androgen-deprivation therapy, a mainstay of prostate cancer treatment, may give prostate cells new growth abilities, scientists at Memorial Sloan Kettering have found.
Large-scale genomics studies have revealed mutations commonly found in patients with prostate cancer, such as FOXA1. Sawyers and team publish a study in Nature confirming that FOXA1 acts an oncogene to drive a subtype of prostate cancer.
Researchers Unravel the Biology of a Distinct Prostate Cancer Subtype
Mutations in a gene called FOXA1 are responsible for a distinct class of prostate cancer tumors, MSK researchers have found.
Study shows that tumor microenvironment can promote prostate cancer progression. This supports the idea that treatments for prostate cancer should consider cells in the tumor surroundings.
A New Approach in Prostate Cancer: Targeting the Cells Surrounding the Tumor
Scientists have found a protein that empowers prostate tumors to resist hormone therapy.
Two studies published in Science describe how prostate cancer cells gain features that make them unresponsive to antiandrogen treatment. In one case, they undergo “lineage plasticity” acquiring mutations that allow them to become a different cell type. In other, prostate cancers can arise from a subtype that does not respond to androgen therapy.
MSK Researchers Discover How Cancer Cells Change Identity To Escape Therapies
Researchers learn how prostate cancer cells change their type to survive treatment.
The gene ASCL1 is critical for controlling lineage plasticity during the switch to the aggressive neuroendocrine prostate cancer. Knowing this can help improve treatment and prevention of prostate cancer.
New Insights Show ASCL1’s Role in Neuroendocrine Prostate Cancer, an Aggressive and Treatment-Resistant Type
Read about a powerful research model developed by MSK researchers to learn how the most common type of prostate cancer changes into a deadly form.
Thyroid Cancer: Genomic Data Changes Treatment Paradigms
Dr. James Fagin laid groundwork to understand the molecular features of thyroid cancer. He and colleagues identified genetic differences underlying thyroid cancer subtypes, which has changed our thinking about thyroid cancer pathology, tumor classification, and treatments. Clinical trials emerging from this work have resulted in new therapies to halt and manage thyroid cancer.
Mutational profiling of thyroid cancers showed that thyroid cancers are associated with high activity of RTK/RAS/BRAF signaling proteins, driven mainly by mutations in BRAF (2003). As an early member of HOPP, Dr. James Fagin and colleagues observed that selective inhibitors against BRAF might halt thyroid cancer. They developed disease models that helped establish that the BRAF inhibitor selumetinib could restore response to radioactive iodine after treatment.
Published landmark clinical trial establishes selumetinib for treatment of metastatic thyroid cancers that are resistant to radioactive iodine therapy. Restoring sensitivity to an existing therapy, known as redifferentiation, is a strategy being tested in other tumor types.
Drug Shown to Reverse Radioiodine Resistance in Some Advanced Thyroid Cancers
The experimental drug selumetinib may allow some patients with advanced thyroid cancer to overcome resistance to radioiodine (RAI), the most effective therapy for the disease, according to new research from Memorial Sloan Kettering Cancer Center.
Dr. Fagin and colleagues published the first comprehensive genomic analysis from patients who developed thyroid cancer after exposure to radiation from Chernobyl, offering insight into how thyroid cancers emerge.
Study Reveals Genetic Causes for Thyroid Cancer Increase after Chernobyl
The study of some victims exposed to ionizing radiation from the 1986 Chernobyl nuclear power plant accident is yielding new information about how radiation-induced thyroid cancer develops.
Dr. Fagin is awarded a prestigious NIH grant (SPORE in Thyroid Cancer) to support research and clinical translation of new therapies for thyroid cancer.
As part of an international effort to catalogue hallmark mutations that are specific to different cancers, MSK publishes a landscape analysis of papillary thyroid carcinomas.
Clinical trials using combined targeted therapies or immunotherapies are available for patients with rare thyroid cancers such as RET-driven tumors and anaplastic thyroid cancer.
Biological Insights Fuel Novel Treatments for Rare Head and Neck Cancers (Part 2: Rare Thyroid Cancers)
This article is Part 2 of our three-part series on MSK-led advances for improving outcomes for patients with rare head and neck cancers.
IDH Mutant Cancers: From Gene Mutation to Approved Therapies
HOPP investigators have contributed fundamental insight into the genes and molecules that regulate cell metabolism, including the IDH genes. Their work has led directly to new and better therapies for acute myeloid leukemia and glioma.
Mutations in IDH1 and IDH2 were known to be associated with metabolic changes in acute myeloid leukemia and malignant glioma. Two studies co-led by HOPP investigators and published in the journal Nature reveal that changes in a gene called IDH are also found in several cancers including colon, prostate, leukemias and brain tumors. Mutations in IDH change the epigenome – how DNA is organized in the cell.
Studies Show How Certain Gene Mutations May Promote Cancer
Two Memorial Sloan Kettering studies provide new clues about genetic mutations that affect cell behavior and play a role in several types of cancer.
The drug enasidenib is used to treat people with AML that have a mutation in the gene IDH2, but some patients stop responding or don’t respond to the drug. HOPP Investigators discovered that some patients show additional genetic changes that allow cancer cells to escape treatment. This discovery allowed doctors to monitor patients for the changes and switch patients to a drug that works in a different way.
Findings from Two Patients Shed New Light on Drug Resistance in AML
A team at MSK has discovered a previously unknown type of resistance to a new leukemia drug.
Findings from People with Acute Myeloid Leukemia Point to a New Understanding of Drug Resistance
Drug resistance is a formidable challenge in cancer treatment. A drug called enasidenib (Idhifa®) was approved by the US Food and Drug Administration last year for the treatment of people with a form of acute myeloid leukemia (AML) that’s driven by a mutation in the gene IDH2. About 15 percent of people with AML have this mutation. Research led by Memorial Sloan Kettering Cancer Center (MSK) reports that people who take enasidenib can develop resistance to it — in a way never seen before. Enasidenib works differently than most cancer drugs. Rather than killing leukemia cells, it turns them into normal blood cells. The discovery of this unique resistence may lead to more-precise treatments for people with AML in the future.
HOPP investigator Ingo Mellinghoff helped bring the first targeted therapy for low-grade diffuse glioma, vorasidenib, to the clinic. Mellinghoff led early clinical trials that were published in the New England Journal of Medicine.
FDA Approves Drug for Low-Grade Glioma With IDH Gene Mutation
A new drug could be an effective treatment for some people with low-grade glioma.
Targeted Therapy Delays Growth for IDH-Mutant Glioma
Neuro-oncologist Ingo Mellinghoff, MD, FACP discusses how his research has led to a new targeted therapy for IDH-mutant glioma – and details how this may mark a paradigm shift in therapeutic options for patients with brain tumors.
Discovery of ESR1 Mutations Results in Precision Therapy for Breast Cancer
Dr. Sarat Chandarlapaty led studies that described how mutations in the ESR1 gene caused some breast cancers to stop responding to treatment. He and colleagues later developed a liquid biopsy (blood based tumor sequencing test) to identify patients with the ESR1 mutations, allowing breast cancer patients with these mutations to be treated using the FDA approved drug elecastrant.
Dr. Chandarlapaty discovered activating mutations in the gene ESR1, explaining how mutations in this signaling protein could cause some breast cancers to become resistant to treatment.
Dr. Chandarlapaty and colleagues developed a method to test for ESR1 mutations in breast cancer patients using a liquid biopsy (circulating tumor cells in blood plasma). This established presence of ESR1 mutations among ~30% of breast cancer patients and that these mutations were associated with poorer outcomes.
The drug elacastrant is a selective estrogen receptor degrader (SERDs) approved for treatment of advanced or metastatic breast cancer in patients who have a mutation in the ESR1 gene.
MSK Discovery of ESR1 Gene Mutation Leads to Approval of Breast Cancer Drug Elacestrant
Learn how an MSK lab discovery in 2013 paved the way for the approval of a new breast cancer drug 10 years later.
The Center for Molecular Oncology: Putting Precision Oncology into Practice
Buoyed by MSK’s success treating “exceptional responders”, the Center for Molecular Oncology (CMO) is established through a generous $100M gift from the Henry and Marie-Josée Kravis Foundation, with Dr. David Solit named its first Director. This also marks the launch of the MSK-IMPACT tumor sequencing assay, developed by Dr. Michael Berger, which allows oncologists to understand the molecular changes in a patient’s tumor, and then provide treatments targeted at those specific changes, also known as precision oncology. Dr. Nikolaus Schultz leads growth of cBioPortal to enable more researchers to use cancer data resources at MSK and worldwide.
Henry and Marie-Josée Kravis Foundation gift $100M to found the Center for Molecular Oncology.
Landmark Gift of $100 Million from the Marie-Josée and Henry R. Kravis Foundation Will Support Groundbreaking Approach to Precision Oncology
Memorial Sloan Kettering launched the Marie-Josée and Henry R. Kravis Center for Molecular Oncology, an ambitious initiative to improve cancer care and research through genomic analysis.
MSK leads landmark publication of the first basket trial in the New England Journal of Medicine.
Increasing numbers of users join cBioPortal.
Charles Sawyers leads launch of AACR Project GENIE.
Memorial Sloan Kettering Cancer Center Researchers Publish Landmark “Basket Study”
Researchers from Memorial Sloan Kettering Cancer Center (MSK) have announced results from the first published basket study, a new form of clinical trial design that explores responses to drugs based on the specific mutations in patients’ tumors rather than where their cancer originated.
MSK publishes landmark analysis of first 10,000 patients to undergo the innovative MSK-IMPACT clinical sequencing test (Berger)
The FDA approves the first use of a targeted therapy that emerges from a basket trial study
2017 MSK-IMPACT is the first sequencing-based laboratory diagnostic test to receive FDA authorization
AACR Project GENIE first data release: 19,000 samples; viewed using cBioPortal
Landmark Analysis from Memorial Sloan Kettering Reveals Genomic Tumor Sequence of More Than 10,000 Cancer Patients Using MSK-IMPACT™
Memorial Sloan Kettering (MSK) has reached a major milestone in bringing personalized treatments to more cancer patients. Michael Berger, PhD, Ahmet Zehir, PhD, and colleagues have reported an in-depth analysis of the first 10,336 patients whose tumors were submitted for clinical genomic sequencing by MSK-IMPACT™, a powerful diagnostic test developed at MSK to provide detailed genetic information about a patient’s cancer.
FDA Announces First Approval of Targeted Therapy Based on Basket Study
The US Food and Drug Administration (FDA) has announced that it has approved the drug vemurafenib for the treatment of patients with BRAF V600-mutant Erdheim-Chester disease (ECD). This is the first approval of a targeted therapy based on a basket study and the first-ever drug approved for ECD, a rare blood disorder. This landmark approval came as a direct result of research at Memorial Sloan Kettering Cancer Center (MSK).
New York State approves MSK ACCESS, a test for deep sequencing of 146 cancer genes using liquid samples.
MSK-ACCESS Receives New York State Approval for New Molecular Assay
Memorial Sloan Kettering Cancer Center (MSK) today announced that the New York State Department of Health has issued approval for a new molecular assay, Analysis of Circulating cfDNA to Evaluate Somatic Status (MSK-ACCESS). MSK-ACCESS was developed within the Marie-Josee and Henry R. Kravis Center for Molecular Oncology (CMO) and the test has been clinically validated and implemented by members of MSK’s Molecular Diagnostics Service.
OncoKB is a knowledge base used to evaluate emerging precision oncology therapies. OncoKB curators provide recommendations for treating genetically defined tumors based on defined “Levels of Evidence”. OncoKB is the first genetic database to achieve partial recognition from the US Food and Drug Administration (FDA).
A Milestone for Precision Oncology: FDA Gives Green Light to MSK’s Genetic Database
OncoKB, a database developed and maintained by investigators at MSK, helps match patients with targeted therapies based on the mutations found in their tumors.
KRAS – From Fundamental Biochemistry to Clinical Trial
KRAS mutations drive many cancers, but mutant KRAS has been elusive and difficult to target because of the protein’s shape. Dr. Piro Lito observed that certain compounds could trap mutant KRAS in a shape that inactivates it, which can restore a cell’s normal function.
KRAS has been called an “undruggable” target because of its structure. Using biochemical approaches, Dr. Piro Lito and team described how a compound (ARS853) traps mutant KRAS in an inactive state.
New Lung Cancer Therapy May Target Previously Untreatable Tumors
Researchers are developing uses for a drug that could benefit many people with lung cancer.
Leptomeningeal Metastasis: A Laboratory Breakthrough Inspired by Patients
While a postdoctoral research fellow, Dr. Adrienne Boire sought to understand how cancer cells spread to other parts of the body. She turned her attention to a poorly understood condition faced by patients with advanced cancer: leptomeningeal metastasis (LM). Dr. Boire discovered that LM cancer cells use iron stores to survive and leads a clinical trial to test whether interrupting this strategy can halt the cancer’s spread.
Adrienne Boire recognized that leptomeningeal cancers secrete factors that make the blood-brain barrier more permeable and enable the cancer cells to survive.
Iron Fiends: Cancer Cells in Brain and Spinal Fluid Survive by Monopolizing a Nutrient
Researchers gain insight into leptomeningeal metastasis, a devastating complication of advanced cancer.
Phase I trial of intrathecal deferoxamine (DFO) is launched to test whether interrupting iron dependence can halt disease progression.
Based on this finding, she launched a clinical trial in 2021 testing whether the iron chelator deferoxamine could be safe and effective for treating LM in cancer patients. Patients receive the drug DFO through a small plastic tube called an Ommaya reservoir inserted into the ventricle which bypasses the blood-brain barrier.
A Phase I Study of Deferoxamine in People with Leptomeningeal Metastasis
Precision Immuno-Oncology: Enhancing the Immune System’s Response to Cancer
HOPP investigators were among the first to describe how mutation load could predict how well a tumor might respond to immunotherapy. Using tumor sequencing data such as MSK-IMPACT, investigators can now predict which features on or within tumor cells make them vulnerable to emerging immunotherapies like cell-based (T-cell) therapies and therapeutic cancer vaccines. The Immuno-oncology Program launched as an independent department at MSK in 2025.
TMB Work: Drs. Timothy Chan and Jedd Wolchok published correlation between higher tumor mutation burden (TMB) and response to immunotherapy in melanoma (NEJM) and in NSCLC (Science). Patients with more mutations “High TMB” responded better to checkpoint inhibitors. They also recognized and confirmed wide, cancer-specific differences in TMB thresholds that would determine response to immunotherapy.
Tumor Mutational Burden Can Help Predict Response to Immunotherapy in Many Different Cancers
Investigators confirmed that people whose tumors have a high tumor mutational burden and were treated with immunotherapy lived longer.
Memorial Sloan Kettering Team Makes Key Discovery in Understanding Immunotherapy’s Successes—And Its Failures
A collaborative team of leaders in the field of cancer immunology has made a key discovery that advances the understanding of why some patients respond to ipilimumab, an immunotherapy drug, while others do not.
Dr. Vinod Balanchandran and team established feasibility of targeting “neoantigens”, (tumour features at the cell surface) in pancreatic cancer, published in Nature in 2017. Balanchandran and colleagues agreed to collaborate with BioNTech in 2019 to develop custom mRNA vaccines that would train a patient’s immune system to recognize and target neoantigen-expressing tumor cells. The therapeutic mRNA vaccine entered Phase trials I in 2022.
Custom mRNA Vaccines for Pancreatic Cancer
Cancer vaccines that use messenger RNA (mRNA) technology are an exciting new approach to develop immunotherapies for cancers with poor prognoses, such as pancreatic cancer.
Started phase 2 trial using therapeutic mRNA vaccine cevumeran in a larger group of patients to determine whether it works better than standard of care to treat cancer patients.
Announced gift to establish the Olayan Center for Cancer Vaccines, Vinod Balanchandran named Director
The Olayan Center for Cancer Vaccines at MSK
Pioneering science and transformative clinical trials to accelerate precision vaccines as the next breakthrough cancer therapy.
HOPP Immuno-Oncology Division becomes the Immuno-Oncology Program and an independent department.
In 2019, HOPP became the research home for a growing number of investigators at MSK focused on translational immuno-oncology. Thanks to ongoing growth and success, the HOPP Immuno-oncology Division became the Immuno-Oncology Program, and independent department that appointed its inaugural Chair, Dr. Andy Minn in 2025.
Andy Minn, MD, PhD, will rejoin Memorial Sloan Kettering Cancer Center as the Inaugural Chair of MSK’s new Immuno-Oncology Program
Andy Minn, MD, PhD, will return to Memorial Sloan Kettering Cancer Center (MSK) as the inaugural Chair of MSK’s new Immuno-Oncology Program in August.
Studies from MSK seeded the development of groundbreaking immunotherapies such as CAR-T cells, which are immune cells engineered to recognize specific features on cancer cell surface and destroy them. However, many solid tumors are not sensitive to CAR-T therapy because they don’t display these external features; they harbor changes inside the cell. HOPP/Immune-oncology member Christopher Klebanoff has built a platform that enables him to look inside cancer cells and target them using engineered T-cell receptor therapies, a technique he compares to x-ray vision.
A New Cellular Immunotherapy Approach May Offer Treatment for AML and MDS
Laboratory research shows how it may be possible to develop an immunotherapy-based approach for treating aggressive forms of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).
