title: Evolutionary strategy for systemic therapy of metastatic breast cancer: balancing response with suppression of resistance.
abstract: Conventional systemic therapy for disseminated breast cancer is based on the general assumption that the greatest patient benefit is achieved by killing the maximum number of tumor cells. While this strategy often achieves a significant reduction in tumor burden, most patients with metastatic breast cancer ultimately die from their disease as therapy fails because tumor cells evolve resistance. We propose that the conventional maximum dose/maximum cell kill cancer therapy, when viewed from an evolutionary vantage, is suboptimal and likely even harmful as it accelerates evolution and growth of the resistant phenotypes that ultimately cause patient death. As an alternative, we are investigating evolutionary therapeutic strategies that shift the treatment goal from killing the maximum number of cancer cells to maximizing patient survival. Here we introduce two novel approaches for systemic therapy for metastatic breast cancer, considering the evolutionary nature of tumor progression; adaptive therapy and double-bind therapy.
authors.affiliation: Department of Cancer Imaging & Metabolism, H Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
authors.forename: Yoonseok
authors.initials: Y
authors.lastname: Kam
authors.forename: Tuhin
authors.initials: T
authors.lastname: Das
authors.forename: Susan
authors.initials: S
authors.lastname: Minton
authors.forename: Robert A
authors.initials: RA
authors.lastname: Gatenby
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005260:Female; D006801:Humans; D009362:Neoplasm Metastasis; D010641:Phenotype; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology; D013997:Time Factors
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000255:Adenosine Triphosphate; D018719:Erb-b2 Receptor Tyrosine Kinases; D020845:Selective Estrogen Receptor Modulators; C508053:ERBB2 protein, human
keywords: adaptive therapy; breast cancer; chemotherapy; double-bind therapy; drug resistance; estrogen; hormonal therapy; tumor evolution