Oncology Abstracts

Endocrine resistant estrogen receptor positive (ER+) breast cancers are dependent upon cyclin-dependent kinases (CDK) 4/6 for proliferation, making them highly suitable for CDK4/6 inhibitor treatment. Despite initial efficacy, acquired resistance to CDK4/6 inhibitors is emerging and is now a major consideration in pre-clinical and clinical drug development. Current models of CDK4/6 inhibitor resistance do not mimic the clinical scenario where CDK4/6 inhibition will occur in th...

Steroid hormone receptors (SHR) play a major role in the normal breast development and breast cancer progression. Estrogen receptor (ER) is expressed in approximately 75% of breast cancers, and the majority of these tumours also express the androgen receptor (AR). While ER-directed therapies have been effective in the majority of patients, a significant subset develops resistance and requires alternative treatment approaches. In the endocrine-resistant setting, emerging insigh...

Estrogen Receptor (ER) signalling, upregulation of the cyclin/CDK pathway, and suppression of p53 form a critical axis controlling proliferation of ER positive breast cancer. In this setting, mutation of p53 is relatively rare and suppression of p53 function can be achieved via regulators MDM2 and MDMX. Activation of p53 by inhibition of MDM2 is a promising therapeutic target in p53 wildtype tumours and several drugs are currently in clinical trials. We hypothesised that the M...

Seventy percent of breast cancers are classified as estrogen-receptor positive (ER+) and ER is the key proliferative driver in these tumours. Clinically, ER+ patients receive ER-targeted (endocrine) therapies to inhibit ER activity and whilst these agents reduce the risk of recurrence, up to 43% patients develop drug resistance within 15 years. Hence, identification of mechanisms underlying these resistant mechanisms could extend the use of endocrine-therapies. Profound altera...

Introduction: Resistance to endocrine therapy is a major clinical problem in estrogen receptor positive (ER+) breast cancer. The androgen receptor (AR) is expressed in ~90% of all primary ER+ breast cancers and high expression of AR is associated with a better patient outcome in this tumours. However, uncertainty surrounding the role of AR in endocrine resistance is reflected in current clinical trials in which both AR agonists and antagonists are being investigated. Here, we ...