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@sigtrans-sttt.bsky.socialSep 20, 2026, 6:00 AM

How does #HCC withstand #OxidativeStress during therapy?

This study identifies a HIF1α–KLF4–hemoglobin axis that scavenges ROS and promotes sorafenib resistance, revealing a targetable redox adaptation.

#STTT #OpenAccess: doi.org/10.1038/s413...

#TumorHypoxia #TherapyResistance #CancerBiology

HIF1α-KLF4 signaling dictates extra-erythrocyte expression of hemoglobin conferring sorafenib resistance in hepatocellular carcinoma
@alicefrolov.bsky.socialSep 14, 2026, 5:03 PM

Sharing a visualization from our ongoing modeling work on intratumoral oxygen dynamics and the HIF-1α-driven transcriptional response.

#TumorHypoxia #HIF1alpha #TumorMicroenvironment #Angiogenesis #OxygenSensing #VEGF #ComputationalOncology #CancerMetabolism

Sharing a visualization from our ongoing modeling work on intratumoral oxygen dynamics and the HIF-1α-driven transcriptional response. Figure: "Oxygen tension collapse drives coordinated hypoxia-angiogenesis program across the tumor radius" Subtitle: "Simulated intratumoral pO₂ gradient from vessel wall to necrotic core with HIF-target activation" The figure uses a horizon-style stacked area representation (layered oxygen-gradient contour strip) to render pO₂ as a function of radial distance from the perfused vessel wall toward the necrotic core. Each contour band encodes a discrete oxygen tension interval, with marker overlays indicating the activation thresholds of canonical HIF-1α target loci. I want to emphasize that the underlying data are simulated; the parameterization reflects diffusion-limited oxygen distributions consistent with published Krogh-cylinder estimates and the well-characterized ~100–200 µm diffusion limit. The central observation is the coordinated character of the transcriptional program along the radial axis. Proximal to the vessel wall, pO₂ remains above the threshold for prolyl hydroxylase domain (PHD/EGLN) activity, sustaining VHL-mediated HIF-1α degradation. As oxygen tension declines toward the intermediate perinecrotic zone, PHD activity becomes substrate-limited, HIF-1α escapes hydroxylation and proteasomal turnover, and it accumulates to drive HRE-dependent transcription. The marker overlays illustrate the staggered engagement of glycolytic effectors (SLC2A1, LDHA), pH-regulatory targets (CA9), and pro-angiogenic signaling (VEGFA) as the gradient steepens. The horizon-strip format was chosen deliberately to compress the steep radial pO₂ decay into a legible vertical encoding while preserving the coincidence between tension thresholds and target activation.