November 23, 2020
Wheeler DA, Takebe N, Hinoue T, Hoadley KA, Cardenas MF, Hamilton AM, Laird PW, Wang L, Johnson A, Dewal N, Miller V, Piñeyro D, Castro de Moura M, Esteller M, Shen H, Zenklusen JC, Tarnuzzer R, McShane LM, Tricoli JV, Williams PM, Lubensky I, O’Sullivan-Coyne G, Kohn EC, Little RF, White J, Malik S, Harris L, Weil C, Chen AP, Karlovich C, Rodgers B, Shankar L, Jacobs P, Nolan T, Hu J, Muzny DM, Doddapaneni H, Korchina V, Gastier-Foster J, Bowen J, Leraas K, Edmondson EF, Doroshow JH, Conley BA, Ivy SP, Staudt LM. Molecular Features of Cancers Exhibiting Exceptional Responses to Treatment. Cancer Cell. 2021 Jan 11;39(1):38-53.e7. doi: 10.1016/j.ccell.2020.10.015. Epub 2020 Nov 19. PMID: 33217343; PMCID: PMC8478080.
A small fraction of cancer patients with advanced disease survive significantly longer than patients with clinically comparable tumors. Molecular mechanisms for exceptional responses to therapy have been identified by genomic analysis of tumor biopsies from individual patients. Here, we analyzed tumor biopsies from an unbiased cohort of 111 exceptional responder patients using multiple platforms to profile genetic and epigenetic aberrations as well as the tumor microenvironment. Integrative analysis uncovered plausible mechanisms for the therapeutic response in nearly a quarter of the patients. The mechanisms were assigned to four broad categories-DNA damage response, intracellular signaling, immune engagement, and genetic alterations characteristic of favorable prognosis-with many tumors falling into multiple categories. These analyses revealed synthetic lethal relationships that may be exploited therapeutically and rare genetic lesions that favor therapeutic success, while also providing a wealth of testable hypotheses regarding oncogenic mechanisms that may influence the response to cancer therapy.
Declaration of Interests P.W.L. is a member of the Scientific Advisory Board for AnchorDX. H.S.’s husband is part of the Scientific Advisory Board for AnchorDX. N.D. is employed by Foundation Medicine and holds Roche stock. A.J. was an employee of and had ownership interest in Foundation Medicine. V.M. was an employee of and had ownership interest in Foundation Medicine (through 12/31/2019) and is an equity shareholder of Mirati Therapeutics, Inc; on the Board of Directors, compensated by and an equity shareholder of Revolution Medicines, Inc.; a part-time employee and equity shareholder of EqRx (since March 2020); and holds patents with the USPO: 8501413, 8067175 (held by Sloan-Kettering Institute for Cancer Research and licensed to Molecular MD). All other authors declare no competing interests.
SINGAPORE, 7 July 2022 – MiRXES Pte Ltd, a Singapore-headquartered biotechnology company, whose mission is to save and improve lives through early, actionable, and personalized diagnoses with its innovative RNA-powered cancer early detection solutions, announced today the signing of a Memorandum of Understanding (MOU) that launched Project CADENCE (CAncer Detected Early caN be CurEd). Project CADENCE is the world’s first large-scale clinical research project for the discovery and validation of novel combinations blood-borne circulating microRNA (miRNA) and DNA methylation biomarkers that will lead to the development of a multi-cancer early detection test for up to nine high incidence and high mortality cancers, including lung, breast, colorectal, liver, stomach (gastric), esophageal, ovarian, pancreatic, and prostate cancers.
A new national consortium – the Consortium for Clinical Research and Innovation, Singapore (CRIS) – has been officially launched by the Minister for Health Mr Ong Ye Kung on 6 April 2022 CRIS brings together five key national R&D, clinical translation and service initiatives that will advance clinical research and innovation for Singapore, and establish important capabilities for a future-ready healthcare system