MDM2 inhibition in combination with endocrine therapy and CDK4/6 inhibition for the treatment of ER-positive breast cancer
Neil Portman, Heloisa H Milioli, Sarah Alexandrou, Rhiannon Coulson, Aliza Yong, Kristine J Fernandez, Kee Ming Chia, Ensar Halilovic, Davendra Segara, Andrew Parker, Sue Haupt, Ygal Haupt, Wayne D Tilley, Alex Swarbrick, C Elizabeth Caldon, Elgene Lim
BREAST CANCER RESEARCH | BMC | Published : 2020
BACKGROUND: Resistance to endocrine therapy is a major clinical challenge in the management of oestrogen receptor (ER)-positive breast cancer. In this setting, p53 is frequently wildtype and its activity may be suppressed via upregulation of its key regulator MDM2. This underlies our rationale to evaluate MDM2 inhibition as a therapeutic strategy in treatment-resistant ER-positive breast cancer. METHODS: We used the MDM2 inhibitor NVP-CGM097 to treat in vitro and in vivo models alone and in combination with fulvestrant or palbociclib. We perform cell viability, cell cycle, apoptosis and senescence assays to evaluate anti-tumour effects in p53 wildtype and p53 mutant ER-positive cell lines (M..View full abstract
Awarded by National Breast Cancer Foundation
Awarded by Cancer Institute of New South Wales
Novartis Australia (NP, HM, EL); National Breast Cancer Foundation (NP: IIRS19-053, EL: EC17-002 and PRAC14-02); Cancer Institute of New South Wales (HM: ECF171156); Breast Cancer Trials - Australia and New Zealand (EL); The Estate of the late RT Hall (AS); Love Your Sister (EL).