KRAS (KRAS proto-oncogene GTPase)

The authors discuss adverse event management and the implications for integration into routine clinical practice. Clinicians caring for patients with low-grade serous ovarian carcinoma can use the drug knowledge and evidence outlined in this review to assist with implementing avutometinib and defactinib therapy.

Outcomes of patients with BCRLM differ through surgical strategies that showed high variability across countries, centers and eras. There is a need for common definition of BCRLM and guidelines for managing patients including transplant option.

Analytical performance was validated in cancer cell lines and in patient-derived fresh frozen tissues, showing complete concordance with Nanopore sequencing and droplet digital PCR (ddPCR) within the evaluated cohort (n = 16). This work introduces a robust and modular PEC biosensing strategy that combines molecular WT suppression with enzyme-free photoelectrochemistry, offering an economically competitive and instrumentation-simplified approach for clinically relevant KRAS mutation analysis toward decentralized testing.

However, the inconsistency in clinical responses across tumor types highlights that mutation alone is not sufficient to predict therapeutic outcomes. This Perspective introduces a multidimensional framework that uniquely integrates KRAS mutational status with tissue, co-mutation, signaling, and immune context to inform rational trial design, predictive biomarker development, and the advancement of KRAS-targeted therapies.

The use of complex dendrimer systems allows precise modulation of membrane-targeted interactions and intracellular signaling, providing mechanistic insights into overcoming EGFREx19Del-driven resistance. Overall, these findings highlight the translational potential of integrating membrane-targeted nanotherapeutics with EGFR-directed therapies to improve outcomes in NSCLC patients.

We evaluated KRAS G12D -specific (MRTX1133) and pan-KRAS inhibitor (RMC-6236) in KRAS mut organoid and orthotopic PDX models of AA. Additionally, KRAS inhibition remodels TME and may enhance innate immune signaling. These findings support continued clinical development of KRAS inhibitors in AA and provide a rationale for combination strategies targeting resistance pathways and stromal remodeling.

The models achieved over 90% accuracy and identified solvent-exposure and conformational changes at residues G10, E62, and H95 as key predictors of treatment resistance. This workflow offers a generalizable strategy for understanding and forecasting mutation-induced resistance.

Although CSF1R inhibition alone was insufficient to improve tumor control, combinatorial blockade of PD-L1 and CD73 augmented systemic antitumor responses, and the addition of CSF1R inhibition in this context further enhanced both local and distant tumor control. These findings identify a CSF1-dependent myeloid resistance program that constrains ablation-induced systemic immunity and demonstrate that rational combination immunotherapy can potentiate the systemic efficacy of tumor ablation in PDAC.

These findings distinguish this lesion from established entities of intrahepatic biliary cystic neoplasms, including intraductal papillary neoplasm, intraductal tubulopapillary neoplasm, intraductal oncocytic papillary neoplasm, and mucinous cystic neoplasm. We propose the designation "eosinophilic biliary cystic neoplasm of the liver" for this distinct intrahepatic biliary neoplasm.

Modelling mutation order indicates that early loss of both APC copies increasingly favours an APC-first pathway with age, while KRAS activation is equally likely to initiate events in younger individuals. Spatial transcriptomics highlights phenotypic heterogeneity among KRAS mutant clones, with mixed lineage presentation observed only in a subset, a state linked to elevated transformation risk in other organs.

Conversely, p53 suppression enables progenitor cell expansion, epithelial-mesenchymal reprogramming, and immune-privileged niche formation. These findings position the progenitor-like state at the convergence of cancer-driving mutations, plasticity, and tissue remodeling, revealing a critical window for intercepting malignancy.