Swiss Oncology and Cancer Immunology Breakthrough Platform (SOCIBP) for Precision Oncology
Prof. Rubin leads an SPHN-PHRT program with co-leads Holger Moch (UHZ), George Coukos (CHUV/UNIL), and Gunnar Rätsch (ETHZ), in collaboration with Olivier Elemento (Englander Institute for Precision Medicine). This Swiss Federal Government-funded project addresses a critical scientific gap in immuno-oncology, while simultaneously developing important molecular oncology tools. Despite the rapid acceleration of novel targeted and immunology-based therapies for cancer, tumor cell resistance remains one of the greatest unmet challenges. SOCIBP will both provide important new tools for the Swiss and international research community, and give insight into the mechanism of resistance for immuno-oncology.
Understanding non-canonical phosphatidylinositol kinases in the maintenance of prostate metabolism
Unlike other tissue types, prostate cell growth and development is heavily dependent on the androgen receptor (AR) signaling pathway. However, other effectors work in conjunction with AR to coordinate key alterations to androgen-dependent tumor biology. In this SNSF-funded project, we are exploring the function of a family of poorly understood lipid kinases called the type II phosphatidylinositol-5- phosphate 4-kinases (PI5P4Ks), and posit that the PI5P4Ks have roles in the control of cellular metabolism that could be pivotal in the regulation of AR in prostate tissue. We are the first group to profile the type II PIP kinases in prostate cancer and will thus establish the foundation for understanding the roles of PI5P4K isoforms in prostate cell biology.
Towards a precision therapy for Speckle-type POZ protein (SPOP) mutant prostate cancer
This project is funded by the Swiss Krebsliga Association in collaboration with Ruedi Aebersold’s laboratory (ETHZ). The focus of this study is to understand the downstream effectors of SPOP, recurrently mutated in 10% of primary prostate cancer patients, through targeted proteomics, and to help develop clinical biomarkers. Our overarching hypothesis is that SPOP mutant prostate cancer will respond distinctly to targeted therapy due to its inherent vulnerabilities. Other areas of SPOP biology are supported by an NCI grant in its 9th year.
Towards understanding and modulating neuroendocrine transdifferentiation in prostate cancer
This project seeks to understand the underlying biology of neuroendocrine prostate cancer (NEPC), which will help create therapeutic approaches that can delay or inhibit this terminal form of prostate cancer and lead to earlier co-targeted therapies prior to disease progression.
Role of m6A methylation in post-transcriptional regulation and prostate cancer disease progression
m6A methylation of mRNAs can alter RNA stability, protein translation efficiency, and patterns of alternative splicing. The aim of the project is to investigate the frequency of m6A in prostate cancer and its functional consequences for the progression of the disease. It is the first study to examine how prostate cancer utilises this alternative molecular mechanism to regulate gene and protein expression. It will provide valuable fundamental research that will contribute to a better understanding of the molecular functioning of prostate cancer.