{"doi":"10.3390/cancers16020257","title":"Testing Adaptive Therapy Protocols Using Gemcitabine and Capecitabine in a Preclinical Model of Endocrine-Resistant Breast Cancer","abstract":"Adaptive therapy, an ecologically inspired approach to cancer treatment, aims to overcome resistance and reduce toxicity by leveraging competitive interactions between drug-sensitive and drug-resistant subclones, prioritizing patient survival and quality of life instead of killing the maximum number of cancer cells. In preparation for a clinical trial, we used endocrine-resistant MCF7 breast cancer to stimulate second-line therapy and tested adaptive therapy using capecitabine, gemcitabine, or their combination in a mouse xenograft model. Dose modulation adaptive therapy with capecitabine alone increased survival time relative to MTD but not statistically significantly (HR = 0.22, 95% CI = 0.043–1.1, p = 0.065). However, when we alternated the drugs in both dose modulation (HR = 0.11, 95% CI = 0.024–0.55, p = 0.007) and intermittent adaptive therapies, the survival time was significantly increased compared to high-dose combination therapy (HR = 0.07, 95% CI = 0.013–0.42, p = 0.003). Overall, the survival time increased with reduced dose for both single drugs (p < 0.01) and combined drugs (p < 0.001), resulting in tumors with fewer proliferation cells (p = 0.0026) and more apoptotic cells (p = 0.045) compared to high-dose therapy. Adaptive therapy favors slower-growing tumors and shows promise in two-drug alternating regimens instead of being combined.","journal":"Cancers","year":2024,"id":437604,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9507,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1170424,"name":"Ruthanne Teo","orcid":null,"position":1,"is_corresponding":false},{"id":1169927,"name":"Luke Foster","orcid":"0000-0002-1496-8851","position":2,"is_corresponding":false},{"id":1169928,"name":"Daniel Saha","orcid":"0000-0001-5103-2465","position":3,"is_corresponding":false},{"id":230220,"name":"Lida A. Mina","orcid":"0000-0003-2606-9922","position":4,"is_corresponding":false},{"id":242415,"name":"Donald W. Northfelt","orcid":"0000-0002-5850-0118","position":5,"is_corresponding":false},{"id":897010,"name":"Karen S. Anderson","orcid":"0000-0002-3870-5730","position":6,"is_corresponding":false},{"id":433863,"name":"Darryl Shibata","orcid":"0000-0002-4567-1639","position":7,"is_corresponding":false},{"id":255974,"name":"Robert A. Gatenby","orcid":"0000-0002-1621-1510","position":8,"is_corresponding":false},{"id":225145,"name":"Luis Cisneros","orcid":"0000-0002-7890-1269","position":9,"is_corresponding":false},{"id":965899,"name":"Brigid V. Troan","orcid":"0000-0003-2212-2167","position":10,"is_corresponding":false},{"id":280735,"name":"Alexander R.A. Anderson","orcid":"0000-0002-2536-4383","position":11,"is_corresponding":false},{"id":267111,"name":"Carlo C. Maley","orcid":"0000-0002-0745-7076","position":12,"is_corresponding":false},{"id":962378,"name":"Sareh Seyedi","orcid":"0009-0006-3263-2055","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T02:00:34.490087Z","pmid":"38254748","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":[]}