Searchable abstracts of presentations at key conferences in oncology

oa0001p001 | (1) | PacRim7

S phase dysregulation occurs following resistance to CDK4/6 inhibition ER+ breast cancer

Alexandrou Sarah , Milioli Heloisa Helena , Portman Neil , Lee Christine , Fernandez Kristine , Blake David , Lim Elgene , Caldon C Elizabeth

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...

oa0001p011 | (1) | PacRim7

The WinPro study: A window of opportunity study of endocrine therapy with and without prometrium in postmenopausal women with early stage hormone receptor-positive breast cancer

Chen Julia , Carson Emma , Segara Davendra , Parker Andrew , O'Toole Sandra , Coates Alan , Mann Bruce , Lindeman Geoffrey , Tilley Wayne , Lim Elgene

There is bidirectional interplay between PR and ER in human breast cancers. There is evidence for a reprogramming of ER chromatin binding sites with 470 genes differentially regulated by dual treatment with estrogen plus progestogen compared to estrogen alone in breast cancer cell lines. Functionally, there was an additive anti-cancer effect with the addition of natural progesterone to endocrine therapy in preclinical breast cancer models. This is a phase II multi-site, random...

oa0001p034 | (1) | PacRim7

Androgen receptor activation in Endocrine-Resistant ER-positive breast cancer

Milioli Heloisa Helena , Chia Kee Ming , Portman Neil , Yong Aliza , Tarulli Gerald , Selth Luke , Tilley Wayne , Hickey Theresa , Lim Elgene

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...

oa0001p040 | (1) | PacRim7

Unravelling the role of cell plasticity in BrCa development and metastasis

Juan Beatriz Perez San , Zadeh Soroor , Ganju Vinod , Vargas Cristina , O'Toole Sandra , Lim Elgene , Davis Melissa , Chaffer Christine

The plastic cancer cell model establishes that genetically identical cancer cells undergo bi-directional conversions between the highly aggressive tumour-initiating (TIC) state and the non-TIC cell state. We have identified subpopulations of breast cancer cells that readily switch from the non-TIC to TIC state, through activation of the EMT transcription factor ZEB-1. We have shown that non-TICs of basal BrCa are uniquely endowed with this plastic phenotype due to the cell&#14...

oa0001p045 | (1) | PacRim7

Single-cell transcriptomics reveals marked heterogeneity for intrinsic molecular subtype and cellular function in estrogen receptor positive breast cancer

Roden Daniel , Wu Sunny , Harvey Kate , Chan Chia-Ling , Al-Eryani Ghamdan , Cazet Aurelie , Lim Elgene , Swarbrick Alexander

Breast cancer is a heterogeneous disease that can be classified into a number of molecular subtypes that predict prognosis and influence clinical treatment. Cellular heterogeneity is also evident within breast cancers and plays a key role in their development, evolution and metastatic progression. How clinical heterogeneity relates to cellular heterogeneity is poorly understood. We have approached this question using single-cell RNA-Seq on 1000s of individual cells from well-e...

oa0001p043 | (1) | PacRim7

Activation of p53 in combination with endocrine and CDK targeted therapies in ER+ breast cancer

Portman Neil , Milioli Heloisa , Yong Aliza , Coulson Rhiannon , Alexandrou Sarah , Lam Natasha , Haupt Sue , Haupt Ygal , Caldon C Elizabeth , Lim Elgene

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...

oa0001p049 | (1) | PacRim7

DNA demethylation agents as a therapeutic approach in endocrine-resistant breast cancer

Stirzaker Clare , Chia Kee Ming , Portman Neil , Milioli Heloisa Helena , Clifton Samuel , Achinger-Kawecka Joanna , Nair Shalima , Lim Elgene , Clark Susan J

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...

oa0001p012 | (1) | PacRim7

Targeting AR in endocrine-resistant breast cancer

Chia KeeMing , Milioli Heloisa , Portman Neil , Laven-Law Geraldine , Coulson Rhiannon , Yong Aliza , Segara Davendra , Parker Andrew , Caldon Catherine E , Deng Niantao , Swarbrick Alexander , Tilley Wayne D , Hickey Theresa E , Lim Elgene

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 ...