ArticleGenome research2017
Genome-wide chemical mutagenesis screens allow unbiased saturation of the cancer genome and identification of drug resistance mutations.
Article in Genome research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Base editing screens define the genetic landscape of cancer drug resistance mechanisms.Nature genetics · 2024Article
- In vitro evolution and whole genome analysis to study chemotherapy drug resistance in haploid human cells.Scientific reports · 2024Article
- Resistance to obinutuzumab-induced antibody-dependent cellular cytotoxicity caused by abnormal Fas signaling is overcome by combination therapies.Molecular biology reports · 2022Article
- Comparative Analysis of Proteomic of Curcumin Reversing Multidrug Resistance in HCT-8/VCR Cells.Journal of oncology · 2022Article
- A Fifteen-Gene Classifier to Predict Neoadjuvant Chemotherapy Responses in Patients with Stage IB to IIB Squamous Cervical Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Review
- From Phenotypic Hit to Chemical Probe: Chemical Biology Approaches to Elucidate Small Molecule Action in Complex Biological Systems.Molecules (Basel, Switzerland) · 2020Review
- MAP2K1 is a potential therapeutic target in erlotinib resistant head and neck squamous cell carcinoma.Scientific reports · 2019Article
- Coupling chemical mutagenesis to next generation sequencing for the identification of drug resistance mutations in Leishmania.Nature communications · 2019Article
- Article
- Gain- and Loss-of-Function Screens Coupled to Next-Generation Sequencing for Antibiotic Mode of Action and Resistance Studies inAntimicrobial agents and chemotherapy · 2019Article
- Mouse models in the era of large human tumour sequencing studies.Open biology · 2018Review
- Targeted inhibition of histone H3K27 demethylation is effective in high-risk neuroblastoma.Science translational medicine · 2018Article
- Pathway-based dissection of the genomic heterogeneity of cancer hallmarks' acquisition with SLAPenrich.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
23 authors at 4 institutions in 5 countries.
Funding
Abstract
Drug resistance is an almost inevitable consequence of cancer therapy and ultimately proves fatal for the majority of patients. In many cases, this is the consequence of specific gene mutations that have the potential to be targeted to resensitize the tumor. The ability to uniformly saturate the genome with point mutations without chromosome or nucleotide sequence context bias would open the door to identify all putative drug resistance mutations in cancer models. Here, we describe such a method for elucidating drug resistance mechanisms using genome-wide chemical mutagenesis allied to next-generation sequencing. We show that chemically mutagenizing the genome of cancer cells dramatically increases the number of drug-resistant clones and allows the detection of both known and novel drug resistance mutations. We used an efficient computational process that allows for the rapid identification of involved pathways and druggable targets. Such a priori knowledge would greatly empower serial monitoring strategies for drug resistance in the clinic as well as the development of trials for drug-resistant patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.