MSK-IMPACT^® (Integrated Mutation Profiling of Actionable Cancer Targets) is a targeted tumor sequencing test used to detect gene mutations and other critical genetic alterations in both rare and common cancers. Developed within the Marie-Josée and Henry R. Kravis Center for Molecular Oncology (CMO) and launched in 2014, the ultimate goal of the MSK-IMPACT^® test is to use clinical molecular testing to improve oncologists’ ability to treat people with solid cancers by giving them a better understanding of the genetic underpinnings of each patient’s illness. MSK-IMPACT^® is designed to detect alterations in 505 cancer-associated genes and is the first laboratory-developed tumor-profiling test to receive authorization from the U.S. Food and Drug Administration. The MSK-IMPACT^® Heme test uses the same technology as MSK-IMPACT^® to look for mutations and other important molecular changes in blood cancers, including leukemia, lymphoma, and multiple myeloma.

The MSK-ACCESS^® (Analysis of Circulating cfDNA to Evaluate Somatic Status) assay is a comprehensive liquid biopsy test that offers noninvasive cancer genomic profiling and disease monitoring. It involves the deep sequencing of 146 key cancer-associated genes selected from MSK’s solid tumor genomic-profiling assay, MSK-IMPACT^®. MSK-ACCESS^® is designed to detect genetic alterations in cfDNA (cell-free DNA) specimens, such as blood and other body fluids. MSK-ACCESS^® was developed within the Marie-Josée 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 in 2019, after receiving approval from the New York State Department of Health.

MSK’s Early Drug Development (EDD) Service is a team of doctors, nurses, and researchers exclusively dedicated to leading early-stage clinical trials of new therapies. In the past five years, the team has pioneered trials that resulted in eight FDA approvals of new targeted therapies. MSK-IMPACT^® and MSK-ACCESS^® are central to the EDD’s ability to identify MSK patients who would be good candidates for early-stage clinical trials. The team receives real-time notifications of sequencing results, which allows them to enroll patients quickly and begin their treatment without delay. The EDD has made historic breakthroughs, including leading the clinical trials that brought a new, highly effective drug for non-small cell lung cancer to patients with a specific gene mutation, as well as spearheading the development of the first-ever drug to act on a mutation in KRAS, a gene that is mutated in more than 25% of cancers and has long been considered impossible to target. The EDD also had a lead role in the development of the first drugs to receive FDA-authorization for a specific mutated gene irrespective of cancer type.

OncoKB™ is a precision oncology knowledge base developed at Memorial Sloan Kettering Cancer Center that contains biological and clinical information about genomic alterations in cancer. Alteration- and tumor type-specific therapeutic implications are classified using the OncoKB™ Levels of Evidence system, which assigns clinical actionability to individual mutational events.  OncoKB™ was developed and is maintained by the Marie Josée and Henry R. Kravis Center for Molecular Oncology at Memorial Sloan Kettering Cancer Center. In 2021, the FDA granted partial recognition to OncoKB, making it the first database of its kind to receive this designation. The National Comprehensive Cancer Network also references OncoKB in its guidelines for treating non-small cell lung cancer and uterine cancer.

Genetic counseling and cancer risk assessment is an important part of cancer care at Memorial Sloan Kettering. Based on genetic test results (such as MSK-IMPACT^® ) and family cancer history, the Clinical Genetics Service (CGS) provides patients and family members with recommendations for surveillance and risk reduction. CGS’s aim is to provide people who have cancer and their family members understand how a diagnosis of cancer in one family member may impact the health of others. Knowing that a genetic predisposition to cancer exists in a family can help identify other relatives who are at risk for the disease. This knowledge can lead to cancer prevention and early intervention for entire families. Researchers in MSK’s Robert and Kate Niehaus Center for Inherited Cancer Genomics use a number of research methods to discover new pathways associated with inherited cancer risk. The Niehaus Center’s ultimate goal is to develop new approaches for precision cancer prevention and earlier detection as well as targeted treatments.

MSK is home to a first-of-its-kind clinic for clonal hematopoiesis (CH), a condition driven by a genetic mutation in blood stem cells. People with CH are at higher risk of blood cancer and cardiovascular disease and have increased cancer mortality rates. MSK researchers were the first to discover the genetic basis of CH and link it to cancer. In the years since, researchers have mined genomic sequencing data collected through the CMO to build predictive models that can identify who is at the highest risk of progressing from CH to blood cancer. These patients are monitored at MSK to spot early signs of progression and intervene as soon as possible. At the same time, MSK scientists are conducting research to develop targeted therapies that can act on mutated stem cells while they are still benign, intercepting cancer before it ever starts.

Data science and computational oncology quickly became institutional priorities at MSK following the establishment of the CMO. These fundamental disciplines are essential to helping our researchers and doctors learn from each patient’s data and translate this knowledge into clinical practice. With philanthropic support, MSK established the Computational Oncology Service in 2018. It has since grown into a highly successful and deeply collaborative cross-departmental research effort that attracts top-tier talent to MSK. Computational teams lead their own studies and support the work of others at MSK, using artificial intelligence and other analytics methods to identify trends in patient demographics, disease progression, responses to therapy, and outcomes that would otherwise likely go undetected.

The Functional Genomics Initiative (FGI) was founded as a direct response to MSK-IMPACT®. Laboratory researchers involved in the program leverage the huge volume of information gleaned from tumor analyses to better understand how individual mutated gene included in the MSK-IMPACT® and MSK-ACCESS® assays promote cancer development and treatment resistance. To advance this work, the FGI makes a series of grants to basic and translational scientists each year, allowing MSK researchers to quickly pursue promising leads arising from the CMO genomic data as they strive to learn more about the genes and proteins that facilitate cancer growth, spread, and response to treatment. Scientists affiliated with the FGI have helped drive the continual expansion of the number of genes covered by MSK-IMPACT® by making recommendations for new additions based on emerging research at MSK and in the field.

MSK’s Global Biomarker Development Program is a nexus for liquid biopsy research and clinical validation. Since 2017, the program has helped accelerate the creation, approval, and routine clinical use of new liquid biopsy-based biomarker assays and technologies that promise to improve clinical decision-making.

From its initial work on tests for people with prostate cancer, the program has dramatically expanded and now includes more than 60 MSK doctors and scientists. Its unique operational model relies on partnerships with biotechnology and pharmaceutical companies that are developing biomarker tests. Support from these partners allows our team to advance their own research efforts while working to validate outside assays and determine their clinical utility, a critical step toward FDA approval.

Founded in 2015, the Robert and Kate Niehaus Center for Inherited Cancer Genomics has become an unsurpassed translational research program for understanding, managing, and preventing inherited cancers. MSK-IMPACT® data plays a major role in the center’s efforts to identify inherited causes of cancer and help families understand and reduce their risk and has been integral to pivotal studies published by the center. Findings made through the Niehaus Center are shaping screening recommendations and have changed MSK’s approach to genetic testing for the family members of people with cancer.

CMO investigators analyze tumor genomic profiling data and clinical information on metastatic events and outcomes from over 25,000 patients with 50 different cancer types, to investigate if a tumor’s genetic mutations can predict whether and where cancer will spread. While some mutations are found to be slightly more common in tumors prone to certain metastatic events, no single mutation or group of mutations could predict with absolute certainty where a particular tumor would metastasize. The researchers find that some mutations, called DNA copy-number changes, are more common in metastatic tumors than in primary tumors, and these changes are predictive of metastatic potential when found in primary tumors. The dataset is being made publicly available to other researchers who wish to explore the relationship between genomic events and cancer progression.

MSK News Article Journal Article

In a new study, a team of investigators is reporting how information about inherited genetic mutations (called germline mutations) can be combined with data from mutations found only in tumors (called somatic mutations) to create a deeper understanding of how tumors grow. In the paper, published November 5, 2021, in Nature Genetics, the researchers explain that the influence of germline mutations on each patient’s cancer is varied and based on multiple factors.

MSK News Article Journal Article

For certain types of cancer, knowing one’s precise genetic ancestry can be important for properly assessing genetic risk factors for the disease and weighing possible treatments. CMO computational biologists show that data from MSK-IMPACT® — which sequences only a subset of genes in the human genome — can be used to reliably establish someone’s genetic ancestry. They also identify a discrepancy in the rates of clinically actionable alterations in patients of African ancestry versus patients of European ancestry as determined by MSK’s OncoKB® database, due to which patients of African ancestry had, on average, fewer options for drugs matching those alterations.

MSK News Article Journal Article

• Deep-Learning Model for Tumor-Type Prediction Using Targeted Clinical Genomic Sequencing Data Cancer Discov, 2024
• Quantifying the Expanding Landscape of Clinical Actionability for Patients with Cancer Cancer Discov, 2024
• Tracking tumour evolution in glioma through liquid biopsies of cerebrospinal fluid Nature, 2019
• Widespread Selection for Oncogenic Mutant Allele Imbalance in Cancer Cancer Cell, 2018
• Genome doubling shapes the evolution and prognosis of advanced cancers Nat Genet, 2018
• HER kinase inhibition in patients with HER2- and HER3-mutant cancers  Nature, 2018
• Therapy-Related Clonal Hematopoiesis in Patients with Non-hematologic Cancers Is Common and Associated with Adverse Clinical Outcomes Cell Stem Cell, 2017
• OncoKB: A Precision Oncology Knowledge Base JCO Precis Oncol, 2017
• Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients  Nat Med, 2017
• Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations  N Engl J Med, 2015

2014: The Marie-Josee and Henry R. Kravis Center for Molecular Oncology (CMO) is established with a landmark gift

The Marie-Josée and Henry R. Kravis Center for Molecular Oncology (CMO) is named in honor of Marie-Josée and Henry R. Kravis, whose transformative gift of $100 million will make it possible to realize the promise of precision oncology and support the development of new, individualized cancer therapies and diagnostic tools. To support these goals, the CMO establishes two unique laboratories: one for cell-free DNA (cfDNA) and the other for computational oncology.

The Cell-free DNA Laboratory is created in collaboration with the Department of Pathology and Laboratory Medicine to respond to the growing interest in non-invasive diagnosis and monitoring of disease in cancer patients.

The CMO Computational Oncology Lab houses teams who lead their own studies and support the work of others at MSK, using artificial intelligence and other analytics methods to identify trends in patient demographics, disease progression, responses to therapy, and outcomes that would otherwise likely go undetected. Read More

2014: MSK-IMPACT® is launched by the CMO and the Molecular Diagnostic Service (MDS)

The Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT®) sequencing test is developed to detect gene mutations and other critical genetic aberrations in both rare and common cancers. The test results give MSK physicians the ability to match people with targeted agent based on the individual tumor’s molecular profile, guide treatment choices and can identify people who are candidates for clinical trials testing targeted therapies.

The Cell-free DNA Laboratory is established

In collaboration with the Department of Pathology and Laboratory Medicine, the CMO establishes the Cell-free DNA Laboratory. Detection of circulating cell-free DNA (cfDNA) in body fluids is of growing interest for non-invasive diagnosis and monitoring of disease in cancer patients.

2015: Centralizing Genomic Data

To facilitate in-depth analysis of clinical MSK-IMPACT data, the CMO creates a centralized resource for investigators to data mine – promoting the ideation of new research questions. The cBioPortal for Cancer Genomics is an open source, interactive analysis and visualization tool designed by MSK scientists to make data from large-scale cancer genomics projects more interpretable and accessible. In 2015, the American Association for Cancer Research (AACR) launches Project GENIE which builds upon the infrastructure and concept of the cBioPortal. AACR Project GENIE is a publicly accessible cancer registry of clinico-genomic data gathered from leading international cancer centers. MSK is the lead contributor of data to the AACR Project GENIE. Read More

2015: MSK Researchers Publish Landmark “Basket Study”

Researchers at Memorial Sloan Kettering pioneer the concept of basket trials that test therapies on tumors regardless of where they originate in the body, as they may carry the same genetic mutations. MSK investigators carry out a histology-independent early phase 2 “basket” study of vemurafenib in patients with nonmelanoma cancers harboring BRAF V600 mutations and observe preliminary vemurafenib activity in non–small-cell lung cancer and in Erdheim–Chester disease and Langerhans’-cell histiocytosis. MSK investigators demonstrate that histologic context is an important determinant of response in BRAF V600–mutated cancers. Read More

2017: MSK-IMPACT: FDA Authorized Test profiles 10,000 Patients

The U.S. Food and Drug Administration (FDA) authorizes the MSK-IMPACT® test for analyzing patient tumors. Michael Berger, PhD, Ahmet Zehir, PhD, and colleagues analyze data from the first 10,336 patients profiled by MSK-IMPACT®. The study found that 37% of their patient cohort had at least one mutation that could be targeted by a therapeutic drug available in a clinical trial or as standard of care, leading to streamlined care and enrollment into clinical trials. Read More

2018: WES Recapture and Analysis                      

The CMO initiates a large-scale project to conduct Whole Exome Sequencing (WES) on DNA leftover from prior MSK-IMPACT tests. The CMO Computational Science (CCS) team develops and launches a novel analysis pipeline to meet the need for analysis of this WES dataset. Later in 2020, a repository is created to enable sharing of the WES Recapture dataset with all MSK investigators and facilitate analysis.

2019: MSK-ACCESS® Receives New York State Approval

The ‘MSK-Analysis of Circulating cfDNA to Evaluate Somatic Status (ACCESS)’ test is developed and tested in the CMO Technology Innovation Lab. MSK-ACCESS® is a liquid biopsy assay that profiles circulating cell-free DNA (cfDNA) from the blood plasma of cancer patients to non-invasively study somatic tumor alterations. In 2019, the New York State Department of Health approves the MSK-ACCESS® assay for clinical use. Concurrently, the MSK-ACCESS® assay is offered as a liquid biopsy test in the Molecular Diagnostic Service. Read More

2020: 50,000 patients are profiled by MSK-IMPACT®

Technicians from the Molecular Diagnostics Service at MSK analyze samples from over 50,000 patients by Next Generation tumor genetic testing such as MSK-IMPACT® and MSK-ACCESS®, that look for cancer-causing mutations (changes) in the genome. Read More

2021: Precision Oncology Knowledge Base (OncoKB) receives FDA Recognition

The U.S. Food and Drug Administration grants partial recognition to the CMO’s Oncology Knowledge Base: OncoKB. OncoKB becomes the first tumor mutation database to be included in the Public Human Genetic Variant Databases. Read More

2022: Studies on cancer progression and genetic ancestry expand our understanding of cancer treatment

CMO investigators analyze tumor genomic profiling data and clinical information on metastatic events and outcomes from over 25,000 patients with 50 different cancer types, to investigate if a tumor’s genetic mutations can predict whether and where cancer will spread. The researchers find that some mutations, called DNA copy-number changes, are more common in metastatic tumors than in primary tumors, and these changes are predictive of metastatic potential when found in primary tumors. Read More

For certain types of cancer, knowing one’s precise genetic ancestry can be important for properly assessing genetic risk factors for the disease and weighing possible treatments. CMO computational biologists show that data from MSK-IMPACT® can be used to reliably establish someone’s genetic ancestry. They also identify a discrepancy in the rates of clinically actionable alterations in patients of African ancestry versus patients of European ancestry as determined by MSK’s OncoKB® database, due to which patients of African ancestry had, on average, fewer options for drugs matching those alterations. Read More

2023: 100,000 tumor/liquid biopsy samples are profiled by clinical MSK-IMPACT® and MSK-ACCESS®

Technicians from the Molecular Diagnostics Service at MSK analyze over 100,000 tumors by Next Generation tumor genetic testing such as MSK-IMPACT® and MSK-ACCESS®, that look for cancer-causing mutations (changes) in the genome. Read More

2023: The Cancer Data Science Initiative

The Cancer Data Science Initiative (CDSI) announces their first data release containing clinical data elements derived from electronic health records using natural language processing (NLP) methods. This release supports the CDSI’s goal to make clinical data accessible and interpretable to all MSK clinicians and investigators and promotes the generation of new research questions.

2024: CMO Computational Biologists use AI to Predict Tumor Type

Tumor type guides clinical treatment decisions in cancer, but histology-based diagnosis remains challenging. Genomic alterations are highly diagnostic of tumor type but the most accurate methods are not clinically feasible and predict across limited cancer types. CMO computational biologists use AI to develop a highly accurate tumor-type prediction model, designed specifically for clinical implementation. This model relies only on widely used cancer gene panel sequencing data, predicts across 38 distinct cancer types, and supports integration of patient-specific nongenomic information for enhanced decision support in challenging diagnostic situations. Read More