BACKGROUND/AIM: Although CDK4/6 inhibitors have been increasingly used in combination with hormonal agents to treat hormone-receptor positive and human epithelial growth factor receptor 2-negative breast cancer, the mechanism of CDK4/6 inhibitor resistance and its impact on established therapy for post-resistance, especially bevacizumab combined with chemotherapy, are unclear. MATERIALS AND METHODS: Sensitivity of RB knockout MCF7 clones to CDK4/6 inhibitors was evaluated in vitro. One RB knockout clone was subcutaneously implanted in nude mice and the effects of bevacizumab on volume and microvessel density (MVD) of tumors were investigated. RESULTS: Palbociclib did not exhibit antitumor efficacy against the RB knockout tumor, in contrast to the parental MCF7 xenograft model. Bevacizumab significantly exhibited antitumor efficacy and suppressed the MVD both in RB knockout and parental MCF7 xenograft models. CONCLUSION: Bevacizumab inhibited tumor growth by suppressing MVD in the CDK4/6 inhibitor-resistant tumor acquired due to RB loss, suggesting its efficacy also in patients after treatment with CDK4/6 inhibitors. Copyright 2022, International Institute of Anticancer Research.
BACKGROUND/AIM: Although CDK4/6 inhibitors have been increasingly used in combination with hormonal agents to treat hormone-receptor positive and human epithelial growth factor receptor 2-negative breast cancer, the mechanism of CDK4/6 inhibitor resistance and its impact on established therapy for post-resistance, especially bevacizumab combined with chemotherapy, are unclear. MATERIALS AND METHODS: Sensitivity of RB knockout MCF7 clones to CDK4/6 inhibitors was evaluated in vitro. One RB knockout clone was subcutaneously implanted in nude mice and the effects of bevacizumab on volume and microvessel density (MVD) of tumors were investigated. RESULTS: Palbociclib did not exhibit antitumor efficacy against the RB knockout tumor, in contrast to the parental MCF7 xenograft model. Bevacizumab significantly exhibited antitumor efficacy and suppressed the MVD both in RB knockout and parental MCF7 xenograft models. CONCLUSION: Bevacizumab inhibited tumor growth by suppressing MVD in the CDK4/6 inhibitor-resistant tumor acquired due to RB loss, suggesting its efficacy also in patients after treatment with CDK4/6 inhibitors. Copyright 2022, International Institute of Anticancer Research.
Authors: Valerie M Jansen; Neil E Bhola; Joshua A Bauer; Luigi Formisano; Kyung-Min Lee; Katherine E Hutchinson; Agnieszka K Witkiewicz; Preston D Moore; Mónica Valéria Estrada; Violeta Sánchez; Paula G Ericsson; Melinda E Sanders; Paula R Pohlmann; Michael J Pishvaian; David A Riddle; Teresa C Dugger; Wenyi Wei; Erik S Knudsen; Carlos L Arteaga Journal: Cancer Res Date: 2017-03-01 Impact factor: 12.701
Authors: R Condorelli; L Spring; J O'Shaughnessy; L Lacroix; C Bailleux; V Scott; J Dubois; R J Nagy; R B Lanman; A J Iafrate; F Andre; A Bardia Journal: Ann Oncol Date: 2018-03-01 Impact factor: 32.976
Authors: David W Miles; Arlene Chan; Luc Y Dirix; Javier Cortés; Xavier Pivot; Piotr Tomczak; Thierry Delozier; Joo Hyuk Sohn; Louise Provencher; Fabio Puglisi; Nadia Harbeck; Guenther G Steger; Andreas Schneeweiss; Andrew M Wardley; Andreas Chlistalla; Gilles Romieu Journal: J Clin Oncol Date: 2010-05-24 Impact factor: 44.544
Authors: Cristina Guarducci; Martina Bonechi; Luca Malorni; Ilenia Migliaccio; Matteo Benelli; Chiara Biagioni; Giulia Boccalini; Dario Romagnoli; Roberto Verardo; Rachel Schiff; C Kent Osborne; Carmine De Angelis; Angelo Di Leo Journal: NPJ Breast Cancer Date: 2018-11-28