PIK3CA mutation

Primary colonic SRCC is a rare malignant tumor with atypical clinical symptoms, and timely identification and intervention are crucial for improving the prognosis.

Furthermore, ATP6V0D2 knockdown inhibited TNBC cells invasion, migration, and proliferation abilities. ATP6V0D2 acts as a promising indicator for both diagnosis and prediction of outcomes in breast cancer and could potentially be a novel therapeutic target for BRCA.

Our findings suggest that combining immunohistochemistry with NGS offers a more reliable classification of ECs, including 'multiple classifier' cases, which, based on our observations, tend to exhibit aggressive behavior. Additionally, our data highlight the complex genetic background of NSMP ECs, which can facilitate further stratification of tumors within this group and potentially help select patients for dedicated clinical trials.

Recent studies indicate that adding inavolisib, a PI3Kα inhibitor, to palbociclib/fulvestrant benefits patients with endocrine-resistant HR+/HER2- metastatic breast cancer with a PIK3CA mutation. Alpelisib and capivasertib are both US Food and Drug Administration (FDA) approved in combination with fulvestrant in patients with endocrine-resistant HR+/HER2-, PIK3CA-mutant metastatic breast cancer, both with activity in the post-CDK4/6 setting...Toxicity profiles of all agents necessitate careful patient selection. Several mutant-selective and pan-mutant-selective novel inhibitors are under investigation with the potential to improve tolerability and efficacy.

FAVA is a rare, but specific vascular anomaly that is often misdiagnosed with other intramuscular vascular malformations and therefore poses significant management challenges. It is imperative that clinicians have a thorough understanding of FAVA in order to provide proper diagnosis and treatment referrals.

The introduction of antibody-drug conjugates, in specific trastuzumab deruxtecan, has resulted in the best progression-free survival among patients with this subtype of breast cancer...Tucatinib, capecitabine, and trastuzumab combination represent one such promising strategy. With the increasing longevity of these patients, important clinical questions include optimal treatment sequencing, the role of de-escalation of treatment in excellent responders, and the associated financial toxicity. Despite the aggressive nature of this subtype of breast cancer, the outcomes continue to improve for these patients with the evolving treatments.

P2, N=106, Completed, Vanderbilt-Ingram Cancer Center | Active, not recruiting --> Completed

It focuses on the development techniques, docking insight, and structure-activity connections of PI3K-based inhibitors. The findings provide useful insights and future approaches for the development of promising PI3K-based inhibitors.

In our patient with SGC, NGS revealed a GPHN-ALK variant that allowed off-label treatment with alectinib, with a remarkable response in primary and metastatic foci. Similarly, the use of NGS in a cutaneous neoplasm in which no definitive diagnosis could be reached by pathology and which had progressed through standard of care treatment elucidated a PIK3CA mutation in which alpelisib was added and ultimately halted POD. Here, we discuss the use of NGS, future projections, and our recommendations.

P2, N=175, Active, not recruiting, German Cancer Research Center | Recruiting --> Active, not recruiting

P=N/A, N=15, Active, not recruiting, HealthPartners Institute | Recruiting --> Active, not recruiting

Additionally, among patients with ERBB2 mutations and treated with pyrotinib, the HER2-low group may experience superior prognosis when compared to the HER2-0 group...Moreover, we classified HER2-low MBC into three clusters, providing a reference for subsequent treatment with enhanced precision. Our study offers valuable insights into the biology of HER2-low MBC and may provide reference for personalized treatment strategies.

BYLieve showed activity of alpelisib plus fulvestrant with manageable toxicity in patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative advanced breast cancer, after progression on a CDK4/6 inhibitor plus an aromatase inhibitor.

Considering the occurrence of several actionable alterations including a TPM4:NTRK1 fusion reported herein, these results support the use of next-generation sequencing (NGS) including RNA analysis for fusion detection to identify such alterations in patients with MPTs. These findings highlight the importance of comprehensive NGS in MPT research to uncover potential targeted treatment options for these patients.

This report provides the first detailed description of the FNA cytology of LCNEC/SCC, thereby enhancing cytopathologists' comprehension of this tumor. Auxiliary studies, including ICC staining and molecular biology assays, are crucial for accurate diagnosis, therapy, and prognosis.

TP53 mutations found in 82% of ovarian SCC cases. CDKN2A mutations and 9p21.3 loss observed in 54.5% of ovarian SCC cohort.

Moreover, the role of PIK3CA mutations in vascular overgrowth syndromes is explored, alongside emerging targeted therapies, such as PI3K and MEK inhibitors, that promise improved outcomes for patients with these challenging conditions. The integration of histology, molecular diagnostics, and multidisciplinary care remains critical for the accurate diagnosis and optimal treatment of vascular anomalies in the era of precision medicine.

TCCRP is a rare TNBC with inert biological behaviours and good prognosis. We found low infiltration of TILs in the pathological tissue of this case, which may be a characteristic of TCCRP, and the presence of Cancer-Associated Fibroblasts (CAF) in the interstitium of the tumour in this case may have suppressed the anti-tumour immunity to some extent, and further studies on the immune characteristics of the tumour microenvironment (TME) in TCCRP are needed.

The 9-gene panel can detect individual cases with gene mutations indicating poor prognosis. The identification of patients with these special gene mutations has certain implications for the clinical management of them.

Drug screening unveiled that STAT3, HSP, EGFR, and NF-kB might be potential therapeutic targets for FIL. This study provided a valuable cellular resource for exploring the underlying pathogenic mechanisms and developing new targeted therapeutic options for PROS.

P3, N=114, Completed, Swiss Group for Clinical Cancer Research | Active, not recruiting --> Completed | N=185 --> 114

One tumor exhibited MSI-High status and a TMB of 19 mut/Mb. Our results indicate the need for further investigation into the role of FOXO1 as a potential prognostic marker in AGCTs.

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.

SGIC is a histopathologically and molecularly heterogeneous lesion with an overall excellent prognosis. The presence of invasive lesions, as well as lymph node or distant metastasis, has emerged as one of the most critical prognostic factors in SGIC patients.

PIK3CA variants were more frequent in resistant HER2+ BC patients than in responsive patients, with a significant correlation between PIK3CA mutation and a lower pCR rate. PIK3CA variants within exon 9 and 20 (such as Glu545Lys and His1047Tyr respectively) were associated with trastuzumab resistance.

Taken together, these results demonstrate that at physiological glucose concentrations, leptin increases migration of 4T1 and metM-Wntlung cells via shared and distinct effects on energy metabolism, suggesting that the type of TNBC genetic alteration plays a role in differential metabolic regulation of leptin-induced migration.

P3, N=230, Recruiting, Hoffmann-La Roche | Trial completion date: Oct 2028 --> Jan 2028 | Trial primary completion date: Oct 2028 --> Oct 2026

Integrative framework Dyscovr links mutations within cancer drivers to downstream expression changesDyscovr uncovers known and novel targets of cancer-driver genesDyscovr reveals clinically important negative genetic interaction pairingsWeb platform to explore uncovered driver gene-target relationships.

PIK3CA gene mutations, which are often present in advanced HR+ breast cancer, can be targeted by alpelisib...The proportion of HER2-low status patients suggests potential benefits from novel HER2-targeted therapies. These findings highlight the need for routine molecular diagnostics in Chile to improve personalized treatment and address economic and access challenges.

Overall, more than half of the UCs had potentially druggable genetic alterations. The proposed NGS panel permits comprehensive and cost-efficient analysis of UC-specific molecular targets and may be considered in clinical routine.

P2, N=69, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Aug 2025 --> Feb 2025

While cancer expansion ensues from dysregulated growth elicited by these mutations, this effect is likely detrimental to embryonic development and/or survival of multicellular organisms. Although all oncogenic mutations considered here are gain-of-function where five of the six increase activity of the encoded proteins, clonal advancement promotes tumor growth by these genomic changes without conferring selection advantages benefiting the organism or species.

Immune gene expression profiling identified four distinct immune contextures of the TME with unique gene expression patterns and immune infiltration. The classification into distinct immune subgroups may provide important information regarding prognosis and the selection of patients undergoing conventional treatments or immunotherapies.

We report a genome-wide evaluation of co-occurring mutations in MSS CRCs, and suggest that co-mutations can improve the prognostic stratification compared to single mutations alone.

P=N/A, N=100, Recruiting, European Institute of Oncology

Higher levels of HER2 biomarkers in baseline tissue and liquid biopsies, including HER2 status (IHC/ISH), HER2/CEP17 ratio, HER2 ISH signals, HER2 H-score, plasma HER2 (ERBB2) amplification status, HER2 adjusted plasma copy number, and HER2 extracellular domain correlate with antitumor activity (indicated by objective response rate, progression-free survival, and overall survival) of T-DXd. Baseline circulating tumor DNA (ctDNA) analysis suggests antitumor activity of T-DXd in patients who had baseline activating RAS, PIK3CA, or HER2 mutations detected in ctDNA.

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.

The patient underwent laparoscopic total colectomy with abdominoperineal resection and end ileostomy, then received 4 cycles adjuvant chemotherapy of oxaliplatin with capecitabine. This patient was followed up to April 2024 and performed well without abnormalities in serum cancer biomarkers and radiological examinations.

Overall, 73% (8/11) tumors with TSC2 IHC loss and underlying pathogenic alterations in TSC2 showed heterogeneous protein loss, with rare interspersed positively staining tumor cells. These data support TSC2 IHC as a potentially useful assay for the diagnostic workup of renal tumors suspected to belong to the TSC/mTOR-associated subgroups.

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.

This article focuses on the influence and mechanism of PIK3CA gene mutation on the targeted therapy and immunotherapy of CRC, and discusses the potential value and future direction of PIK3CA gene mutation in the personalized therapy of CRC. We aim to provide new perspectives and ideas for the precise diagnosis and treatment of CRC.

Through this endeavor, we identified two novel genes, CNTNAP5 and GATA6, implicated in CRC carcinogenesis. Overall, our findings reveal convincing biomarkers markers for detecting CRAs with a propensity for CRC development, highlighting the importance of early genetic screening in CRC prevention.