ARID1A mutation

Notably, genes commonly mutated in AITL, including RHOA, TET2, DNMT3A, and IDH2, were absent in this case. A review of the literature highlights the heterogeneous genomic landscape of AITL and the diversity of treatment options available, underscoring the importance of tailored approaches to overcome resistance and improve outcomes in this distinct lymphoma subtype.

MeC is a pathological subtype with an active immune response and is a promising group for ICB therapy. This heightened immune response was not limited to the patient's microsatellite status.

Niraparib failed to meet the prespecified efficacy end point for response. However, clinical benefit was suggested in a proportion of patients who had a confirmed mBAP1, supporting further investigation.

Our study supports full molecular classification of UCS. We also raise awareness for potentially assessing POLE mutation allele fraction and clonality in the consideration of classifying a tumor as POLEmut.

However, our newly identified high-risk signature identified 46% of PTR cases at diagnosis. Overall, these results contribute to our understanding of the genomic landscape of patients with primary treatment resistance.

ARID1A mutation correlated with OCCC baseline immune activation. Stromal reconstruction and tumor metabolic reprogramming functioned as key processes of OCCC dynamic progression. VEGF inhibition remodeled OCCC stroma, restored T cell function and potentiated immunotherapy. CD36 and CD47 might be potential therapeutic targets for recurrent OCCC.

P1, N=161, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2025 --> Jan 2026

We conclude that the micropapillary structure is an indicator for unfavorable clinical outcomes in HPVA, and can aid in the prognostic stratification of Silva pattern C EAC. The presence of HER2 amplification and specific gene mutations raise the possibility for targeted therapy in the future.

P1, N=61, Recruiting, Nuvectis Pharma, Inc. | Trial completion date: Jun 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> May 2025

Our study provides a comprehensive characterization of the genomic landscape and clonal evolution in OCCC within a substantial cohort. These findings unveil potentially actionable molecular alterations that could be leveraged to develop targeted therapies.

In the Korean cohort, ICIs were most effective in MSI and EBV cases, showing disease control rates of 100%, compared to 62.9% in GS and 12.5% in CIN subtypes. The NGS method successfully maps the mutational landscape of GC, providing a practical TCGA classification surrogate to optimize patient-specific treatment strategies.

In addition, targeting STAT5 effectively improved anti-PD-1 efficiency in ARID1A-wild type (WT) GC patients. Taken together, ARID1A is a coactivator of STAT5, function as a chromatin organizer in GC ICIs resistance, and targeting STAT5 is an effective strategy to improve the efficiency of ICIs in GC.

The frequent alterations of the PI3K pathway in gynecological cancers could emerge as new treatment target. Our data confirm the high frequency of PIK3CA mutations establishing EC as an ideal candidate for testing of PI3K inhibitors regardless of the TCGA classification. Moreover, these data confirm that other targetable mutations are present also in MSS EC group thus suggesting that new target agents should be explored.

The results of the present study suggested that druggable gene alterations may provide useful information not only in proposing alternative treatment after standard of care but also in selecting second-line targeted treatments after immunotherapy for patients with advanced HCC.

Since genetic alterations of the chromatin pathway genes are important in both UTUC and UCB, they could serve as potential biomarkers for predicting disease progression and therapeutic targets. Differences in mutation frequencies of DDR pathway, TMB, CNV, and TCR might be the contributing factors for the distinct responses to immune checkpoint inhibitor (ICI) between UTUC and UCB.

Polyubiquitinated bands of SOX17 were observed in MG132 treated OVTOKO, but not in OVISE or RMG-V OCCC cells...These findings indicate that SOX17 is not uniformly and heterogeneously expressed in OCCCs, independent of ARID1A deficiency. Impaired ubiquitin-mediated proteasome degradation may stabilize SOX17 in some OCCC cells.

This review explores the multifaceted genetic, epigenetic and microenvironmental drivers of CCA. Understanding these diverse mechanisms is essential for characterizing the complex pathways of CCA carcinogenesis and developing targeted therapies to improve patient outcomes.

Further experiments revealed that the expression of p16 was suppressed in the BR0063-resistant cells via DNA hypermethylation in the CpG island (CGI) promoter region, rather than via PRC2 occupancy. The expression of TET1, which is required for DNA demethylation, was found to be inversely correlated with p16 CGI methylation, and this may serve as a biomarker for the prediction of resistance to PRC2 inhibitors in SWI/SNF LOF tumors.

P1/2, N=37, Terminated, Opna Bio LLC | Phase classification: P2a --> P1/2

Over half of cases with luminal molecular phenotype demonstrate immune-enriched TME, suggesting a potentially significant role for immunotherapy in these patients and expanded efforts in this arena. Using the BG Tumor PortraitTM assay, low TMB and MSS was present in the majority of IBC samples evaluated in spite of numerous studies showing common DNA repair mutations. HER2 expressing cases demonstrated a predominantly immune-desert phenotype and further study of the clinical relevance and validation of this is warranted.

ATMlow in GCs shows a characteristic clinicopathological feature that correlates strongly with ARID1Alow. ATM mutation was also associated with ARID1A mutations, highlighting the interactions between ATM and ARID1A in GC and suggesting a potential therapeutic target.

Our research shows that nuclear-localized mutated ARID1A proteins retain tumor-suppressive function. We identify promising strategies to treat cancers harboring missense mutations in the BAF complex.

Additionally, knockdown of Notch1 blocked the aggressive phenotype induced by recombinant VASN protein. In conclusion, our data uncover the role of VASN in mediating the progression of ARID1A-depleted lung adenocarcinoma and highlight VASN as a promising therapeutic target for this disease.

In conclusion, this retrospective study is the largest series of multiple PSP cases and provides new insights into the genomic underpinning of PSP. This work has a potential to broaden our understanding of the pathogenesis and development of these lesions and warrants analysis in larger cohorts.

This pilot study explores the applicability of LB in GEP-NETs MP evaluation. Further studies with larger cohorts are needed to validate LB and to define the clinical impact.

Notably, we found that FUDR exhibited increased sensitivity in ARID1A-deficient cells compared to 5-fluorouracil (5-FU), a commonly used anticancer drug for CRC. In conclusion, ARID1A loss significantly heightens sensitivity to FUDR by promoting FUDR-induced DNA damage in CRC. These findings offer a novel therapeutic approach for the treatment of CRC characterized by ARID1A loss-of-function mutations.

DNA-based next-generation sequencing revealed a nonsense mutation in SMARCA4, copy number loss in SMARCB1, and a nonsense mutation in ARID1A. Different molecular alterations of the switch/sucrose nonfermenting complex subunits in the present case may provide further insights into the functions of the switch/sucrose nonfermenting complex in the progression of tumors.

Independently of the second mutation, energetic processes and cholesterol metabolism were up-modulated, while the immune response was down-modulated. This work provides a complete molecular signature of HNF1A-associated HAs, analyzing the association between specific HNF1A variants and the development of HA while identifying potential new therapeutic targets for non-surgical treatment.

We believe that AURKAi hold promise as potential therapeutics for ARID1A mutation colorectal cancer patients.

Here we present a case series of metastatic LCNEC in which favorable clinical courses with persistent response periods towards immunochemotherapy with nivolumab/ipilimumab/carboplatin and paclitaxel were achieved. The case series presented here underlines the feasibility and efficacy of combined ICI targeting PD-1 and CTLA-4 in combination with a platinum doublet in metastatic LCNEC. Despite the limited number of cases, we suggest the TMB to be a frequent and potentially characteristic marker in LCNEC that is well known to predict responsiveness towards immunochemotherapy.

This is the largest study to investigate the distinct genomic landscape of CDH1-MT GC. Our data indicated GC patients with CDH1 mutations could potentially benefit from agents targeting PARP and Wee1.

Additionally, it will discuss recent data indicating the potential use of EBV infection as a predictive biomarker of response to chemotherapy and immune checkpoint inhibitors. The review also delves into potential therapeutic approaches for EBVaGC, including targeted therapies and adoptive immunotherapy, highlighting the promising potential of EBV as a therapeutic target.

Our findings collectively provide unprecedented insights into the significance of age and ethnicity on the molecular and clinical characteristics of BC patients.

The sensitivity to chemodrugs (carboplatin, paclitaxel, gemcitabine, doxorubicin, and olaparib) was conducted. Drug testing could reveal the individual PDO's responsiveness to drugs. PDOs might be as valuable resources for investigating genomic biomarkers for personalized treatment.

Our findings expand knowledge on their clinical and molecular features. We present the first molecular profile of primary CNS intraparenchymal EMZL, underscoring the need for further research to understand their biology and optimize treatment strategies.

Further studies showed that RMS PDCs retained the genetic alterations and the expression of RMS hallmark and dependency genes in matched primary tumors and acted as valuable tools to assess drug responses and pharmacogenomic interactions. Our study provides unique PDCs that are available for preclinical studies of RMS and further advances the feasibility of RMS PDCs as valuable tools for developing personalized treatments for patients.

The main differential diagnoses are colorectal adenocarcinoma NOS, mucinous adenocarcinoma and signet ring cell adenocarcinoma. Patients are referred to the RENAPE expert network.

P2, N=30, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2026

These results suggest the existence of an mTOR oncogenic addiction in biliary tract cancer. Our results support the interest in performing exome sequencing in liver cancers and the potential to identify actionable mutations with important therapeutic issues.

Similar to the West, KRAS G12 mutations are the most common, with KRAS G12C nearly twice as common in men than in women. Furthermore, co-existence of EGFR and KRAS mutations occurs approximately 18% KRAS cases representing a diagnostic and therapeutic challenge worthy of further study.

Mutations in other SWI/SNF complex members, including SMARCA2, SMARCB1 and SMARCC1, occur rarely in either OCCC or SCCOHT. Abrogated SWI/SNF raises opportunities for pharmacological inhibition, including the use of DNA damage repair inhibitors, kinase and epigenetic inhibitors, as well as immune checkpoint blockade.

Rather, we find that KEAP1 perturbation exacerbates genome instability phenotypes associated with ARID1A deficiency. Together, our findings identify a potentially novel synthetic lethal interaction of ARID1A-deficient cells.