U-M Rogel Cancer Center

Keratin 9 regulates mechanosensitive YAP1 signalling in palmoplantar epidermis

Steiner et al. propose that keratin 9 (K9) interacts with 14-3-3, sequestering YAP1 in the cytoplasm and inhibiting YAP1 activity. They identify dysregulated YAP in palmoplantar keratinization diseases, with K9 as a downstream regulator of YAP.

RINGSIDE Phase II Study of Varegacestat for Treatment of Desmoid Tumors: A Randomized Dose-Finding Clinical Trial

PURPOSE Desmoid tumors (DTs) are rare, often locally aggressive, connective tissue neoplasms with limited effective treatment options. We evaluated the safety and efficacy of varegacestat, an oral gamma-secretase inhibitor. METHODS RINGSIDE phase II was an open-label, randomized,...

RNF5 Regulates HERP1 and OS9 Stability and Modulates Processing of an ERAD Substrate

Endoplasmic reticulum-associated degradation (ERAD) must dynamically adapt to cellular protein-folding demands, yet mechanisms regulating ERAD-associated adaptors remain incompletely defined. Here, we identify the E3 ubiquitin ligase RNF5 as a regulator of the ERAD adaptors HERPU...

Patient-centred and fit-for-purpose clinical trials in rare cancers: lessons from sarcomas for operationalising 2024 WHO Guidance and ICH E6(R3)

Rare cancers account for approximately one quarter of cancer diagnoses in Europe, yet prevailing clinical trial governance frameworks were developed for common malignancies and conventional randomised designs. The 2024 WHO Guidance for best practices for clinical trials and ICH E...