Profile:
Lukas Kenner is a pathologist and cancer researcher whose research interests center on the molecular mechanisms of cancer initiation, progression, and metastasis. His lab investigates the role of AP-1 and JAK-STAT signaling in cancer development and has developed several gene-targeted mouse models to study new diagnostic approaches and therapies for anaplastic large cell lymphoma (ALCL) and prostate cancer.
In addition to his work on cancer biology, Kenner has also studies the effects of microplastics on colon cancer formation. His research has highlighted the potential adverse health effects of microplastics and has contributed to our understanding of the complex interplay between environmental factors and cancer development. Overall, Kenner’s research aims to translate basic science discoveries into clinical applications for cancer patients, with a focus on developing new strategies for cancer prevention and treatment. His work has led to the development of new mouse models for studying cancer, as well as new diagnostic and therapeutic approaches for ALCL and prostate cancer. Additionally, his research on microplastics has contributed to our understanding of the potential health risks associated with environmental factors.
Talk Title:
Unveiling the Dichotomous Role of STAT3 Signaling in Prostate Cancer Progression and Therapeutic Potential.
Abstract:
Prostate Cancer (PCa), a prevalent male malignancy, often advances to a lethal metastatic stage (mPCa) with unclear underlying mechanisms. Core to mPCa progression is the frequent co-deletion of PTEN and STAT3 genes, as revealed in liquid biopsies. In a Pten-null mouse prostate model, Stat3 loss activates the mTOR/CREB pathway via LKB1/pAMPK reduction, fostering metastatic disease. Contrarily, constitutive Stat3 activation suppresses mTORC1/CREB, preventing mPCa. Interestingly, Metformin, a common anti-diabetic drug, upon treating STAT3/AR-expressing PCa xenografts, significantly curtails tumor growth by inhibiting mTORC1/CREB and lowering AR, PSA levels, underscoring a novel therapeutic avenue for high-grade PCa patients, especially with co-morbid type 2 diabetes. Furthermore, the GP130 receptor, through autonomous activation, triggers Stat3 signaling, markedly reducing tumor growth in vivo by mediating senescence and enhancing anti-tumor immunity through cytotoxic T-cell recruitment. High GP130 mRNA expression in human PCa patients correlates with better recurrence-free survival, highlighting the tumor-suppressive facet of GP130-STAT3 signaling contrary to the existing notion of its blockade for treating malignant PCa. Collectively, these findings illuminate the complex, context-dependent role of STAT3 signaling in PCa, showcasing the potential of targeted modulation of STAT3 and GP130 pathways as innovative therapeutic strategies in mitigating prostate cancer progression and recurrence.