SMAD4 mutation

With the largest IPN/ICPN cohort reported to date, our study provides a genome- and spatial transcriptome-level portrait of sequential carcinogenesis and differences in the anatomical location of biliary papillary neoplasms.

Gallbladder NEC requires standardized treatment. Comparisons with other gallbladder carcinomas revealed clinical phenotypes, molecular alterations, functional characteristics, and enriched pathways.

Understanding the complex interplay between genetic alterations and immune markers is critical for optimizing therapeutic strategies and improving clinical outcomes. Further research is warranted to validate these findings and explore personalized treatment approaches in CRC.

Marked genomic heterogeneity exists among patients with BTCs based on anatomic and geographic location. The overwhelming majority of BTC patients with clinically significant mutations had concurrent genomic co-alterations. The current study highlights the molecular complexity of BTCs with multiple alterations that commonly co-exist and could potentially be targeted to treat BTCs.

In the majority of cases, EUS-FNA/FNB can acquire adequate sample for NGS and identify tumor-specific mutations in patients with pancreatic malignancies. Strict pre-analysis screening criteria may negatively impact the sample adequacy and the success rate for NGS.

Rim enhancement, CBD dilation on contrast-enhanced MRI and higher CA19-9 level are promising radiological and clinical factors for identifying SMAD4-mutated PDAC.

Multi-omics and treatment response data from 115 samples of 49 patients with CRLM undergoing bevacizumab (BVZ)-based chemotherapy show little difference in genomic alterations in 92% of cases, while remarkable differences are observed at the transcriptomic level...Gene interference experiments suggest that SMAD4R361H/C mutations confer BVZ and 5-fluorouracil (5-FU) resistance through STAT3 signaling. Notably, supplementing BVZ and 5-FU with the STAT3 inhibitor GB201 restores therapeutic efficacy in SMAD4R361H/C cancer cells. Our study uncovers the evolutionary dynamics of CRLM and its microenvironment during treatment and offers strategies to overcome drug resistance.

Using integrative analysis, we also detected recurrent alterations in the WNT, TGFB, TP53, IGF2/PI3K, and RTK/RAS pathways. Our study thus advances the molecular profiling of CRC in Hispanics and Latinos; suggests precision medicine therapeutics can be tailored to an underrepresented community; and demonstrates genetic similarity can be an important component in understanding colorectal carcinogenesis.

Moreover, DOX further increases the level of cellular ROS, and the sustained accumulation of ROS ultimately leads to apoptosis of ME2-deficient PC cells. This targeting nanostructure shows potential for enhancing collateral lethality in this PC subgroup.

It might be a predictive and prognostic biomarker or therapeutic target to achieve the desired clinical benefits. Moreover, we discuss potential strategies to implement targeted therapies in terms of SMAD4 genetic status.

The observed phenotypic diversity, particularly in gastrointestinal involvement, underscores the need for tailored clinical approaches. Comprehensive assessments identified associated musculoskeletal and cardiovascular anomalies, emphasizing the systemic nature of HHT-JPS.

Accordingly, the combination of olaparib and radiotherapy was indicated in vivo and in vitro to specifically reduce the growth of SMAD4-deficient PDAC by attenuating PARP1 activity. Collectively, our results revealed a novel molecular mechanism for the involvement of the SMAD4-PARP1 interaction in DNA repair with a vital role in radiotherapy response in PDAC. Based on our set of findings, our findings offer a new combined therapeutic strategy for SMAD4 deficient PDAC that can significantly reduce pancreatic cancer radiotherapy resistance.