Searchable abstracts of presentations at key conferences in oncology

oa0001p052 | (1) | PacRim7

Novel and highly selective CDK9 inhibitors suppress proliferation of triple negative breast cancer (TNBC) cells in vitro

Winter Jean M , Mustafa Ebtihal H , Wang Shudong , Selth Luke A , Hickey Theresa E , Tilley Wayne D

This study evaluates the efficacy of two newly developed selective CDK9 inhibitors (CDK9i) across a panel of TNBC cell lines. MDA-MB-453, MFM-223, MDA-MB-468 and MDA-MB-231 TNBC cells were treated with increasing concentrations of two novel and highly selective CDK9 inhibitors and the effect on proliferation, apoptosis and expression of CDK9 targets determined. MDA-MB-453 and -468 cells showed significant growth inhibition with as little as 150 nM of CDK9i, evident 3 days afte...

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...

oa0001p016 | (1) | PacRim7

AR chromatin binding is reprogrammed in the absence of FOXA1 in ER- breast cancers

Denis Iza , Selth Luke A , Robinson Jessica LL , Mohammed Hisham , Carroll Thomas , Brown Gordon D , Neal David E , Carroll Jason S , Tilley Wayne D , Hickey Theresa E

Introduction: 75% of breast cancers (BCa) are driven by the estrogen receptor α (ER+). Tumours lacking ER (ER-) are more aggressive and have the poorest prognosis. The androgen receptor (AR) is also widely expressed in BCa (90% of primary tumours). FOXA1 is a pioneer factor required for oncogenic AR signalling in PCa but its role in AR signaling in ER-BCa is not clear. We previously showed that cell growth is increased when FOXA1 is overexpressed in AR-driven PCa and BCa ...

oa0001p046 | (1) | PacRim7

A miR-194-regulated transcriptional network is associated with progression to androgen receptor-independent prostate cancer

Fernandes Rayzel C , Dredge Kate , Bert Andrew G , Toubia John , Pillman Katherine A , Gregory Philip A , Hickey Theresa E , Tilley Wayne D , Goodall Gregory J , Selth Luke A

MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression programs and have a critical role in both normal biology and disease. We previously identified microRNA-194 (miR-194) as an important driver of prostate cancer metastasis, although the molecular mechanisms by which it mediates these effects are not well understood. This study aimed to identify target genes and pathways that are responsible for miR-194’s pro-metastatic activity. By integrating tran...

oa0001p014 | (1) | PacRim7

Nuclear ErbB-2 activity modulates the interferon signaling pathway in breast cancer cells resistant to anti-ErbB-2 therapies

Russo Rosalia I Cordo , Madera Santiago , Chervo Maria F , Ebrahimie Esmaeil , Selth Luke , Chiauzzi Violeta A , Kikhtyak Zoya , Proietti Cecilia J , Schillaci Roxana , Charreau Eduardo H , Hickey Theresa E , Tilley Wayne D , Elizalde Patricia V

Overexpression of ErbB-2, a member of ErbB family of receptor tyrosine kinases, occurs in 15–20% of breast cancers (BC) and is considered a major oncogenic driver. Despite clinical efficiency of ErbB-2-targeted therapies (e.g. trastuzumab), resistance to said drugs is a major issue. While ErbB-2 is mainly a cell membrane-bound receptor, it can migrate to the nucleus (NErbB-2) where it acts as a transcription factor or coactivator. We revealed that NErbB-2 is a major proli...

oa0001p036 | (1) | PacRim7

Lipid elongation in prostate cancer: an androgen regulated process and a novel therapeutic target

Nassar Zeyad D , Centenera Margaret M , Machiels Jelle , Zinonos Irene , Hanson Adrienne , Bloch Katarzyna , Mah Chui Yan , Ryan Natalie K , Williams Elizabeth D , Evdokiou Andreas , Tilley Wayne D , Selth Luke A , Butler Lisa M , Swinnen Johannes V

Objective: Although initially effective, androgen deprivation therapy fails to achieve an enduring remission in patients with advanced prostate cancer (PCa) and the cells maintain active androgen receptor (AR) signalling. Hence, a detailed understanding of the AR-driven downstream processes that are required for tumour cell growth and survival, such as lipid metabolism, is essential to reveal new therapeutic targets. In this study, we aimed to evaluate the effect of androgens ...