Timeline of Breakthroughs
Scroll right to see some of the groundbreaking advances that HOPP researchers have pioneered in recent years.
—New Gene Function Discovered
Timothy Chan, Ross Levine, Ingo Mellinghoff, and Craig Thompson labs discover that mutations in certain metabolic enzymes cause cancer by changing how DNA is organized in the cell. The results are published in Nature.
—Exceptional Responders Defined
The Michael Berger, Timothy Chan, David Solit, and Barry Taylor labs link a complete response to the drug everolimus (Afinitor®, Zortress®) to mutations in TSC1. The results, reported in Science, launch the National Cancer Institute’s Exceptional Responders Initiative.
—Prostate Cancer Target Discovered
Charles Sawyers and colleagues solve how the glucocorticoid receptor acts as a bypass in antiandrogen-resistant tumors. The results are published in Cell.
—Breast Cancer Drug Resistance Mutations Discovered
The Michael Berger and Sarat Chandarlapaty labs identify mutations in the ligand-binding domain of the estrogen receptor (ESR1). These results are published in Nature Genetics.
—Genomics Predicts Immunotherapy Response
The Timothy Chan and Jedd Wolchok labs, with collaborators, compare and analyze genetic variations among cancer patients to predict who responds best to anti-CTL4A and anti-PD1 immunotherapy, harnessing the patient’s immune system to fight cancer. The results appear in Science and the New England Journal of Medicine.
—Precision Medicine for Breast Cancer
The Sarat Chandarlapaty and Maurizio Scaltriti labs demonstrate that PI3K pathway inhibition upregulates estrogen receptor function. The results appear in Science Translational Medicine.
—Targetable Mutation Identified
The Michael Berger, Timothy Chan, Ping Chi, James Fagin, and Marc Ladanyi labs discover a novel oncogenic form of the ALK protein in melanoma and thyroid carcinomas, generated from an alternative transcription start site. The results are published in Science.
—Targeted Therapy for Leukemia
The Omar Abdel-Wahab lab treats genetically defined myelodysplastic syndrome and acute myeloid leukemia patients by targeting splicesomal proteins. The results are published in Nature Medicine.
—International Data Sharing Launched
AACR Project GENIE, a multi-institutional, international initiative led by Charles Sawyers launches. The phase I includes the release of genomics data from 19,000 cancer patients, linked to clinical outcomes and shared publicly on an open-source platform. The results are published in Cancer Discovery.
—MSK Clinical Sequencing Assay Established
The Michael Berger, Marc Ladanyi, Nikolaus Schultz, David Solit, and Barry Taylor labs, with others at MSK, assemble 10,000 patients for the MSK-IMPACT project, providing publicly accessible data on clinically relevant genomic alterations. The results are published in Nature Medicine.
—FDA Approval of enasidinib
The FDA approves a new type of therapy to treat AML (IDH2 mutant). The work is a result of collaboration between the Levine, Abdel-Wahab and Thompson labs and published in NEJM 2017.
—FDA Approval of ivosideinib
The FDA approves another therapy to treat AML (IDH1 mutant). The work results from the same collaboration between the Levine, Abdel-Wahab and Thompson labs to develop enasidinib and is published in NEJM 2018.
Certain immunotherapies work better in some cancers but not others. When scientists looked closely at MSK-IMPACT and treatment data, they saw that tumor mutation burden (TMB) is predictive of checkpoint inhibitor success in a cancer-specific manner, a useful decision-making tool when treating patients. The study was published in Nature Genetics and led by Nadeem Riaz, David Solit, Timothy Chan and Luc Morris.
—New Oncogene Discovered
The FOXA1 gene is mutated in ~12% of prostate cancers but its role was unclear. The Sawyers lab show that FOXA1 acts as an oncogene to drive a newly defined subtype of prostate cancers and points towards new targeted therapies to tamper tumor growth.
—New Perspective on Testing
BRCA mutations are known risk factors for breast, ovarian and other cancers but, using computational methods, the Taylor, Berger, and Solit labs show that BRCA1 and BRCA2 mutation context is important: some mutations are drivers while others are just passengers. This knowledge impacts therapeutic decisions. Published in Nature.
—New Therapeutic Insight
The Omar Abdel-Wahab and Barry Taylor labs show that E571K mutations in the XPO1 gene make cancer patients more sensitive to selinexor therapy and then demonstrate why cancer cells with this particular mutation are more sensitive to therapy. Published in Cancer Discovery.
—New Cancer Model
HOPP scientists and colleagues create the first rectal cancer organoid models derived from human tumors, making it easier and faster to test new therapies for rectal cancer in the lab and design better clinical trials. Published in Nature Medicine.
—Scientific Discovery in Prostate Cancer
The Sawyers lab demonstrates that existing prostate cells reprogram to become like stem cells, and then change their features to evade cancer therapy. Published in Science.
—Actionable Target Identified
The Charles Sawyers lab identifies a novel source of drug resistance coming from the tumor environment, NRG1, which promotes growth signals in tumor cells. Drugs targeting these signals can restore sensitivity to antiandrogen drugs and help keep prostate cancers in check. Published in Cancer Cell.
—Scientific Discovery in Metastasis
Adrienne Boire and Dana Pe’er demonstrate how cancer cells survive in the cerebrospinal fluid by reprogramming themselves to monopolize available iron. Published in Science.
—Breakthrough Therapy Designation for Sotorasib
Piro Lito, Neal Rosen, and Bob Li develop a drug that directly and effectively targets the KRAS protein, frequently mutated in cancers, and “freezes” the activity of the K12GC mutant form of KRAS. Published in NEJM.
—Sotorasib is FDA-Approved
—OncoKB receives partial recognition status from the FDA
OncoKB is a knowledgebase that assigns diagnostic, prognostic, and therapeutic predictions to cancer mutations or genetic variants according to defined levels of evidence. It is actively curated by disease experts as new evidence emerges and is a powerful tool for delivering precision oncology. Led by Debyani Chakravarty, Jian Jiong Gao, Nikolaus Schultz and David Solit.