Oncology Abstracts

Background: Elevated circulating macrophage inhibitory cytokine -1/growth differentiation factor 15 (MIC-1/GDF15), interleukins 4 (IL4) and 6 (IL6) levels were associated with poor prognosis and resistance to docetaxel chemotherapy in an exploratory cohort of men with metastatic castration resistant prostate cancer (mCRPC). To establish level 2 evidence of biomarker utility, these cytokines were tested in internal and external validation cohorts.Methods:...

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...

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...

A current challenge in cancer therapeutics is incomplete response to treatment and emergence of therapy-resistant disease. Androgen deprivation therapy (ADT), the standard treatment for advanced prostate cancer, and effectively reduces the tumour burden in most patients. Yet, residual tumour cells that withstand ADT eventually develop lethal castration-resistance. Eliminating these castrate-tolerant cells, by combining ADT with other treatments, might delay or even prevent cas...

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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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...

We have recently discovered that metals which coordinate with selected compounds can be prepared inside liposomes. This technology, which we refer to as Metaplex™ technology, is enabling development of a brand new class of therapeutics. Previously the development of metal drug complexes (CDCs) has been hindered because of their very poor aqueous solubility. As an example, diethyldithiocarbamate (DDC) is the primary metabolite of disulfiram, an approved drug for the treatm...