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...

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...

oa0001p048 | (1) | PacRim7

Exploring the clinical significance of interactions between oestrogen and progesterone receptors in breast and endometrioid adenocarcinomas by proximity ligation assay

Snell Cameron E , Smith Deborah , Gough Madeline , Liu Cheng , Middleton Kathryn , Pyke Christopher , Shannon Catherine , Woodward Natasha , Hickey Theresa E , Armes Jane E , Tilley Wayne D

Recent pre-clinical studies indicate that activated progesterone receptor (PR) (particularly the PR-B isoform) binds to oestrogen receptor-α (ER) and reprograms transcription toward better breast cancer outcomes. We investigated whether ER and PR interactions were present in breast and endometrial tumours and associated with clinical parameters including response to endocrine treatments. We developed a proximity ligation assay to detect ER and PR interactions in formalin-...

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 ...

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...