PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

P1/2, N=53, Not yet recruiting, Shanxi Province Cancer Hospital

The final analysis of the BRIGHT-2 randomized clinical trial confirms improved PFS with the addition of bireociclib to fulvestrant, with manageable safety as a treatment option for patients with HR-positive, ERBB2-negative ABC with progression after prior endocrine therapy. ClinicalTrials.gov Identifier: NCT05077449.

Global sensitivity analysis identified compensatory feedback, tumor proliferation rate, and PI3K-mTOR crosstalk as key determinants of tumor response. This novel QSP application exemplifies an innovative bottom-up modeling approach to support patient selection and dosing strategies for future clinical studies.

Pathological subtypes of CCA exhibit distinct clinical outcomes and molecular characteristics. Classification based on pathological subtype provides a useful framework for understanding the clinical and molecular heterogeneity of CCA.

PAK1/2/3 break-apart fluorescence in situ hybridization (FISH) showed no split signals in any case; PAK3 FISH also failed in the same two older specimens. Thus, IFK may represent a distinct clinicopathologic variant of seborrheic keratosis under our proposed diagnostic criteria.

Somatic PGVs in potentially targetable pathways were found in 72% of ATC tumors. Given the aggressiveness of ATC and the limited efficacy of current treatments, these findings support the rationale for biomarker-driven basket trials investigating the efficacy of targeted therapies in this population.

P1/2, N=17, Completed, Joseph Sparano | Active, not recruiting --> Completed

The greatest increase in the cell migratory capacity was observed for cells carrying the PIK3CA H1047R mutation, which induced the most pronounced mesenchymal phenotype, as well as for PTEN-/- cells, which retained the most epithelial phenotype. Our analysis showed that mutations indirectly affecting the MAPK/ERK pathway and promoting ERK activation have the greatest impact on EMT and cell motility.

P2, N=60, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting

P1, N=30, Recruiting, Hoffmann-La Roche | Trial completion date: Sep 2026 --> Sep 2028 | Trial primary completion date: Sep 2026 --> Sep 2028

Our study is the first to demonstrate that LIE exerts potent antitumor effects against pancreatic cancer cells by inducing apoptosis and inhibiting malignant phenotypes through suppression of the PI3K/AKT pathway. These findings highlight LIE as a promising novel therapeutic candidate for pancreatic cancer treatment.

Biological evaluation showed that compound 26 exhibited high PI3Kα selectivity over PI3Kβ (1268-fold), PI3Kγ (350-fold), and PI3Kδ (206-fold). Further assessment of its pharmacokinetic properties and in vivo efficacy underscored the promising preclinical potential of compound 26.