Oncology Abstracts

Prostate cancers are considered immunologically ‘cold’ tumors as they demonstrate poor response to check-point inhibitor therapy (CPI). Enrichment of interferon gamma (IFNγ) response genes, critical for innate and adaptive immune response to viral infections, have been demonstrated to indicate a positive response to CPI. Tumor IFNγ signaling acts as both an activator and inhibitor of effector T-cell response/trafficking via regulation of Th-1 chemokines (CX...

The exquisite dependency of PCa on androgens for growth and survival was first recognized in the 1940’s when Huggins and Hodges demonstrated the antitumour activity of hormonal manipulation in the treatment of PCa. Since then, androgen deprivation therapy has been the standard of care in the treatment of metastatic and locally advanced PCa. Drugs targeting the androgen/androgen receptor (AR) axis have been well-validated clinically and remain without a doubt the most effe...

Tumour cell heterogeneity constitutes a challenge for cancer treatment and deeply impact the outcome of patients. A simultaneous overview of cancer cells and associated stromal cells is critical for the design of improved therapeutic regimes. Single-cell RNA-seq has emerged as a powerful method to unravel heterogeneity of complex biological systems; this has enabled in vivo characterization of cell type compositions through unsupervised sampling and modelling of trans...

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-...

The establishment of mammographic screening programs has resulted in a striking increase in the incidence of ductal carcinoma in situ (DCIS), with DCIS accounting for approximately 20% of all new screen-detected breast cancers. An estimated 40% to 70% of DCIS lesions may progress to invasive disease if left untreated. This number is considerably reduced by treatment: surgical excision followed by radiation therapy is curative in over 95% of cases. However, of the DCIS...

Epithelial-mesenchymal transition (EMT) and the reverse mesenchymal-epithelial transition (MET) are normal biological processes, however they are also thought to play a critical role in the progression and metastasis of cancers, including breast cancer. Cancer cells reactivate the gene expression programs of EMT and MET through a wide range of mechanisms, and better understanding of these regulatory processes will lead to the identification of therapeutically actionable target...

High breast density is an independent risk factor for breast cancer. There is exciting potential for breast density to become a widespread health assessment tool, used to identify the women most at risk of breast cancer in order to intervene early and reduce that risk. However, a better understanding of causal biological mechanisms that lead to high breast density is required in order to develop therapeutic approaches. This project aimed to identify and investigate biological ...

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Estrogen receptor alpha (ERα) activity is associated with increased cancer cell proliferation. Studies aiming to understand the impact of ERα on cancer-associated phenotypes have largely been limited to its transcriptional activity. Herein, we demonstrate that ERα coordinates its transcriptional output with selective modulation of mRNA translation. Importantly, translational perturbations caused by depletion of ERα largely manifest as ‘translational of...

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