Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células del Manto/tratamiento farmacológico , Oligopéptidos/uso terapéutico , Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico , Adenina/análogos & derivados , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Oligopéptidos/farmacología , Piperidinas , Pirazoles/farmacología , Pirimidinas/farmacologíaAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Síndrome Antifosfolípido , Neoplasias Faciales , Inmunoterapia Adoptiva , Linfoma de Células B Grandes Difuso , Rituximab/administración & dosificación , Anciano , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/diagnóstico por imagen , Síndrome Antifosfolípido/terapia , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Neoplasias Faciales/diagnóstico por imagen , Neoplasias Faciales/terapia , Femenino , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/terapia , Prednisona/administración & dosificación , Vincristina/administración & dosificaciónRESUMEN
Enhanced recovery programs emphasize implementation of perioperative measures to reduce stress and restore baseline function. Complications and length of stay are greatly improved as a result, but the field is moving toward more patient centric and longer term outcomes that better reflect functional recovery. Programs demonstrating value in these domains will undoubtedly see corollary gains in traditional metrics. Thus, greater focus on patient well-being and treatment success is key to successful implementation of enhanced recovery.
Asunto(s)
Neoplasias Colorrectales/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Oncología Quirúrgica/métodos , Humanos , Atención Perioperativa/métodos , Resultado del TratamientoRESUMEN
Significant endocrine therapy-resistant tumor proliferation is present in ≥20% of estrogen receptor-positive (ER+) primary breast cancers and is associated with disease recurrence and death. Here, we uncover a link between intrinsic endocrine therapy resistance and dysregulation of the MutL mismatch repair (MMR) complex (MLH1/3, PMS1/2), and demonstrate a direct role for MutL complex loss in resistance to all classes of endocrine therapy. We find that MutL deficiency in ER+ breast cancer abrogates CHK2-mediated inhibition of CDK4, a prerequisite for endocrine therapy responsiveness. Consequently, CDK4/6 inhibitors (CDK4/6i) remain effective in MutL-defective ER+ breast cancer cells. These observations are supported by data from a clinical trial where a CDK4/6i was found to strongly inhibit aromatase inhibitor-resistant proliferation of MutL-defective tumors. These data suggest that diagnostic markers of MutL deficiency could be used to direct adjuvant CDK4/6i to a population of patients with breast cancer who exhibit marked resistance to the current standard of care.Significance: MutL deficiency in a subset of ER+ primary tumors explains why CDK4/6 inhibition is effective against some de novo endocrine therapy-resistant tumors. Therefore, markers of MutL dysregulation could guide CDK4/6 inhibitor use in the adjuvant setting, where the risk benefit ratio for untargeted therapeutic intervention is narrow. Cancer Discov; 7(10); 1168-83. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 1047.