{"doi":"10.1016/j.tranon.2021.101260","title":"A novel strategy for combination of clofarabine and pictilisib is synergistic in gastric cancer","abstract":"Gastric cancer (GC) is frequently characterized by resistance to standard chemotherapeutic regimens and poor clinical outcomes. We aimed to identify a novel therapeutic approach using drug sensitivity testing (DST) and our computational SynerySeq pipeline. DST of GC cell lines was performed with a library of 215 Federal Drug Administration (FDA) approved compounds and identified clofarabine as a potential therapeutic agent. RNA-sequencing (RNAseq) of clofarabine treated GC cells was analyzed according to our SynergySeq pipeline and identified pictilisib as a potential synergistic agent. Clonogenic survival and Annexin V assays demonstrated increased cell death with clofarabine and pictilisib combination treatment (P<0.01). The combination induced double strand breaks (DSB) as indicated by phosphorylated H2A histone family member X (γH2AX) immunofluorescence and western blot analysis (P<0.01). Pictilisib treatment inhibited the protein kinase B (AKT) cell survival pathway and promoted a pro-apoptotic phenotype as evidenced by quantitative real time polymerase chain reaction (qRT-PCR) analysis of the B-cell lymphoma 2 (BCL2) protein family members (P<0.01). Patient derived xenograft (PDX) data confirmed that the combination is more effective in abrogating tumor growth with prolonged survival than single-agent treatment (P<0.01). The novel combination of clofarabine and pictilisib in GC promotes DNA damage and inhibits key cell survival pathways to induce cell death beyond single-agent treatment.","journal":"Translational Oncology","year":2021,"id":193413,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9481,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":427554,"name":"Shoumin Zhu","orcid":null,"position":1,"is_corresponding":false},{"id":295186,"name":"Rimpi Khurana","orcid":"0000-0002-0493-6266","position":2,"is_corresponding":false},{"id":353035,"name":"Ines Lohse","orcid":"0000-0002-9979-9400","position":3,"is_corresponding":false},{"id":761811,"name":"Silvia Giordano","orcid":"0000-0003-1854-1086","position":4,"is_corresponding":false},{"id":761812,"name":"Simona Corso","orcid":"0000-0002-5069-1503","position":5,"is_corresponding":false},{"id":320998,"name":"Hassan Al‐Ali","orcid":"0000-0002-8899-3443","position":6,"is_corresponding":false},{"id":761813,"name":"Shaun P. Brothers","orcid":"0000-0003-2184-4037","position":7,"is_corresponding":false},{"id":279165,"name":"Claes Wahlestedt","orcid":"0000-0003-4471-5916","position":8,"is_corresponding":false},{"id":64669,"name":"Stephan C. Schürer","orcid":"0000-0001-7180-0978","position":9,"is_corresponding":false},{"id":426787,"name":"Wael El‐Rifai","orcid":"0000-0003-2101-6098","position":10,"is_corresponding":false},{"id":426780,"name":"Shayan Khalafi","orcid":"0000-0001-5208-0581","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-18T23:49:51.300073Z","pmid":"34735897","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}