David P. Labbé, PhD

🚨 New Review in Gene! Therapy-Induced Senescence in Prostate Cancer ✔ Mechanisms & biomarkers ✔ Dual role of TIS: tumor-suppressive vs. tumor-promoting ✔ Senolytics & senomorphics as next-gen strategies ✔ Clinical trials & future directions 🔗 doi.org/10.1016/j.gene.2025.…

Altogether diet and tumor genetics conspire to promote prostate cancer metabolism and shape the tumor microenvironment, take a look at the topnotch commentary by @DanielFrigo on our work! bit.ly/3ReRGga (16/17)

Altogether, the oncogene MYC promotes a broad metabolic reprogramming. Obesogenic HFD not only enhances MYC-driven metabolic vulnerabilities but also induces aerobic glycolysis and lactate accumulation, boosting cancer hallmarks and prostate cancer progression. (13/17)

Critically, tumor acquisition of glycolytic features, characterized by high levels of LDHA is associated with worse prognosis in two independent cohorts (TCGA/PRAD and META855 datasets). (12/17)

Deconvolution models uncovered ⬆️ proportion of M2-like macrophages in ⬆️ glycolytic prostate cancer from patients with ⬆️ saturated fat intake. This strongly suggests that acquisition of glycolytic features contributes to shaping a TME supportive of cancer progression. (11/17)

Interrogation of the prospective HPFS/PHS cohorts that high saturated fat intake, but not BMI, is associated with an enrichment in a glycolysis transcriptional signature in clinical samples. (10/17)

Lactate also promotes tumor cell migration, leading to a greater fraction of motile cells and increased displacement over time. Critically, lactate also potentiates the traction force of cancer cells on the extracellular matrix, in line with a more invasive phenotype. (9/17)

Lactate also promotes vascular tubulogenesis. Inhibiting LDHA (enzyme that catalyzes the conversion of pyruvate to lactate) with FX11, or preventing lactate import with MCT-1/MCT-4 inhibitor syrosingopine, reduced tubulogenesis/organization of capillary-like tubules. (8/17)

Intra-tumoral lactate accumulation is associated with multiple cancer hallmarks, such as immune evasion, serving as fuel for lactate-avid Treg cells and as a stimulator of TAM M2 polarization. (7/17)

Accordingly, obesogenic HFD boost glucose uptake, as evidenced by 18F-FDG uptake in MyC-CaP allografts. Critically, increased aerobic glycolysis has not been a Leitmotiv in localized #prostatecancer but is rather associated with aggressive disease. (6/17)