FGFR2 (Fibroblast growth factor receptor 2)

P1, N=160, Recruiting, SystImmune Inc. | N=120 --> 160

Fusion transcript analysis identified 91 recurrent fusions, including novel partners with ERBB2, MED1, and CDK12, suggesting the possibility of unique molecular events. Interpretation and conclusions This study demonstrates that Indian breast cancer patients exhibit molecular subtypes and actionable mutations comparable to Caucasian cohorts.

Stereotactic biopsy of diffuse brainstem tumors can be performed safely. Identification of targets for personalized therapy may be essential for management of these patients.

Malignant effusion CBs show favourable intra-patient biomarker consistency over time, supporting their feasibility for longitudinal monitoring. Effusion-based testing shows potential value for potentially identifying candidates for FGFR2b-targeted therapies, pending further clinical validation.

While approved pan-FGFR inhibitors provide clinical benefit, their durability is limited by acquired, often polyclonal, on-target resistance mutations affecting key regions of the FGFR2 kinase domain, including the gatekeeper residue (V565), molecular brake residues (N550, E566, K642), and other key variants...Given FGFR2-associated toxicities and the need for subtype selectivity, FGFR4 inhibition was prioritized as a selectivity determinant, while sparing FGFR1 was considered less critical. Guided by structure-based drug design, a reversible aminopyrimidine screening hit was optimized into a novel covalent inhibitor series active against FGFR2 wild-type and clinically relevant resistance mutations. An advanced lead 13 showed favorable potency, ADME properties, and demonstrated proof-of-concept in vivo efficacy in an FGFR2-amplified xenograft model comparable with the standard of care.

This cross-study integrative analysis provides an international view of BTC genomics, codifying how geography, etiology, and anatomical subtype together shape driver landscapes.

Notably, it showed minimal activity in non-FGFR2-dependent cells. This work presents a new class of selective FGFR2 inhibitors based on a novel scaffold, offering promising lead compounds for the development of FGFR2-target therapies.

Existing literature primarily identifies such tumors in the distal extremities and temporomandibular joint; however, the case reported herein is the first documented occurrence in the perineum of a female. This finding suggests that the spectrum of CCMN may extend beyond the traditionally recognized locations of the distal extremities and temporomandibular joint.

The integration of NGS and the subsequent use of matched targeted therapy significantly improved survival outcomes in selected patients with advanced BTC, highlighting the importance of precision medicine strategies.

In contrast to the pheochromocytoma, the BDA showed no evidence of a second TP53 alteration that might suggest that TP53 had played a role in its pathogenesis. This case highlights the rare presentation of pheochromocytoma in LFS and provides a molecular hypothesis of how this tumor may have developed.

Only one patient died 16 months after surgery due to an unrelated traffic accident.