INCISOR: An Algorithm to Identify Synthetic Rescue Mediators of Resistance to Targeted and Immunotherapy

Despite the success of targeted therapies including immunotherapies in cancer treatments, tumor resistance to targeted therapies remains a fundamental challenge. Tumors can evolve resistance to a therapy that targets one gene by acquiring compensatory alterations in another gene, such compensatory i...

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Bibliographic Details
Published inMethods in molecular biology (Clifton, N.J.) Vol. 2381; p. 203
Main Authors Wang, Xiaoman, Vizeacoumar, Frederick Sagayaraj, Sahu, Avinash Das
Format Journal Article
LanguageEnglish
Published United States 2021
Subjects
Algorithms
Humans
Immunotherapy
Molecular Targeted Therapy
Neoplasms - drug therapy
Neoplasms - therapy
Transcriptome
Targeted therapies
Genetic interactions
Treatment resistance
Precision oncology
Synthetic rescue
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Summary:Despite the success of targeted therapies including immunotherapies in cancer treatments, tumor resistance to targeted therapies remains a fundamental challenge. Tumors can evolve resistance to a therapy that targets one gene by acquiring compensatory alterations in another gene, such compensatory interaction between two genes is referred to as synthetic rescue (SR) interactions. To identify SRs, here we describe an algorithm, INCISOR, that leverages tumor transcriptomics and clinical information from 10,000 patients as well as data from experimental screens. INCISOR can identify SRs that are common across several cancer-types in genome-wide fashion by sifting through half a billion possible gene-gene combinations and provide a framework to design therapies to tackle resistance.
ISSN:1940-6029
DOI:10.1007/978-1-0716-1740-3_11