PIK3CA mutation

We characterized the tumor immune microenvironment in patients with advanced-stage ovarian clear cell carcinoma. PD-L1 and CD8+T cell expression significantly increased after recurrence. Whether this could be used to select patients for immunotherapy in the recurrence setting should be investigated.

There are very few studies focusing on genetic mutations in histologically transformed lung cancer. A next-generation sequencing (NGS), in our case, showed PI3KCA mutation along with in-frame deletion of EGFR.

FGFR2 mutations may play a role in tumor recurrence in a subset of low-risk endometrial cancers, underscoring the importance of molecular profiling in identifying patients at risk. FGFR2 represents a potential therapeutic target, warranting further validation in larger cohorts to establish its clinical utility.

This study represents one of the most extensive efforts to characterize SCBC to date, providing a novel understanding of the genomic alterations underlying the disease and revealing actionable mutations that could serve as potential targets for improved clinical outcomes.

Inavolisib plus ET demonstrated a manageable safety profile and encouraging preliminary anti-tumour activity in patients with PIK3CA-mutated, HR-positive, HER2-negative LA/mBC, including those in the post-CDK4/6i setting.

Mutations in adenocarcinomas aligned with the ICPNs. This suggests that ICPN and BilIN are independent at the DNA level and that the presence of ICPNs may not imply risk for subsequent flat dysplasia elsewhere in the biliary tree.

Its key diagnostic features include high-grade basaloid tumor cells associated with shadow cells, tumor necrosis, and diffuse nuclear β-catenin staining. To improve diagnostic accuracy and reduce ambiguity, we propose adopting "pilomatrix-like high-grade endometrial carcinoma" as a standardized term.

This study demonstrates the distinct clinicopathologic and genomic characteristics of TNBC subclassifications. APOBEC activity-related hypermutation is a defining characteristic of the LP group.

P2, N=70, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Mar 2026

In this study, a total of 784 clinically actionable mutations were reported for 1010 patients with genomic sequencing. Of these, 96/1010 (10%) patients had at least one actionable mutation in homologous recombination repair genes (BRCA1, BRCA2, PALB2) and 36/96 (37.5%) patients received PARP inhibitors (33 olaparib and three talazoparib). In addition, 381/1010 (38%) patients had at least one clinically actionable PIK3CA mutation, and 84/381 (22%) received alpelisib. Additionally, 544/1010 (54%) of patients had either AKT1 (41/1010), PIK3CA (381/1010), or PTEN (122/1010) alterations that were FDA approved in November 2023 for capivasertib in the treatment of HR+HER2- metastatic BC (MBC) patients. Furthermore, 144/1010 (14%) patients in this study had at least one ESR1 mutation, a clinically actionable mutation that was FDA approved in January 2023 for elacestrant in the treatment of ER+HER2- MBC patients (44% detected by liquid biopsy). Future studies are needed to determine the efficacy of elacestrant and capivasertib for patients with these mutations, and to tailor strategies for optimal patient quality of life and cancer outcome.

Prognosis correlated with high-risk morphologic features in the adenosarcomatous component, including sarcomatous overgrowth, extensive rhabdomyosarcomatous differentiation, vascular invasion, and high-grade nuclear atypia. "Mixed endometrioid adenocarcinoma and adenosarcoma" is a clonal biphasic malignant neoplasm of uncertain histogenesis, with a high frequency of DICER1 mutations.

Mutations in ESR1 and PIK3CA were recognized by CD4 + T cells from healthy donors through potential restriction by common HLA II alleles. Further studies are warranted to elucidate the landscape of HLA II presentation and validate the clinical applicability of these mutations for the immunotherapy of patients with endocrine-resistant breast cancer.

Importantly, the association between tumoral mutational profile and survival differed by site of metastatic disease. The prognostic significance of specific mutations, particularly BRAF and KRAS, differs between patients with CPM and CLM, and supports the distinct biology of these metastatic sites and the importance of tissue and circulating genomic profiling to risk-stratify these patients according to site of metastasis.

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

Notably, germline carriers exhibited lower PIK3CA mutation rates than non-carriers. These findings advance our understanding of Thai breast cancer genomics and underscore the importance of ethnic diversity in cancer research, offering insights into tailored screening and therapeutic approaches.

Our findings further establish CYLD-mutant anal SqCC as an infrequent but distinct clinicopathologic entity with characteristic pathogenetic features and a possible association with adverse clinical outcomes. Among HPV-positive anal SqCC, CYLD mutation represents a potentially useful novel marker for this distinct entity and cylindroma-like morphology serves as a useful feature to identify such cases.

P1/2, N=28, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | N=106 --> 28

P2, N=24, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jul 2025 --> Oct 2027

One case showed loss of 3p material with SETD2 gene mutation and gain of PIK3CA gene, similar to our case. As thymic NB is extremely rare, report of more genetically characterized cases should help to delineate their pathobiology and shed light on possible mechanisms involved in the associated SIADH syndrome.

IL7R expression is a vital prognostic marker in high-grade gliomas. The radiomics-based LR models demonstrate strong predictive capabilities for patient outcomes. Future investigations should aim to incorporate these insights into clinical practice to enhance personalized treatment approaches for patients with high-grade glioma.

For those with PIK3CA or AKT1 mutation or PTEN inactivation, combination therapy with the AKT pathway inhibitor capivasertib is recommended. Alpelisib, the first AKT1 inhibitor approved in combination therapy with fulvestrant in PIK3CA mutated tumors only, is now less in favor given its challenging side effect profile. When mutations are not present, options include combination therapy with the mTOR inhibitor everolimus or changing endocrine therapy and continuing a CDK 4/6 inhibitor...Optimal sequencing of treatment options depends on several factors: (1) the presence of specific molecular aberrations; (2) previous treatment history, duration of response and patient's performance status; (3) balance between maximizing survival benefits with quality of life/toxicities; (4) disease burden. In the upcoming years, we anticipate FDA approvals for more of the SERD molecules both in monotherapy and in combination therapy which will continue to expand the options available for HR + /HER2- MBC patients.

Our study expands on the clinical and pathologic spectrum and provides the first molecular data on these unusual neoplasms. Further, we provide a comprehensive review of the literature of all previously reported cases and briefly discuss relevant differential diagnoses and their molecular features.

Validation experiments confirmed the essential role of NEDD8, NEDD8-MDP-1, and NAE1, indicating a novel regulatory mechanism in PIK3CA E545K-mutated HNSCC. Our findings suggest that PIK3CA mutation may serve as a predictive biomarker for neddylation inhibitor therapy in a subpopulation of HNSCC.

These results provide a spectrum of genomic alterations in young Chinese women and highlight different frequencies of gene variants in young Asian patients versus Western patients with breast cancer. Further research should explore the biological mechanism to provide more treatment strategies for young Asian women.

This exploratory interim analysis demonstrated the rapid onset of hyperglycemia in patients receiving alpelisib, even with the ITACA trial's dietary interventions. Proactive monitoring, within the first week after initiation of treatment, and early management of hyperglycemia are crucial in this patient population.

Furthermore, our investigation revealed that pharmacological inhibition of PI3K sensitized cancer cells to TTFields, both in vitro and in vivo. Our research suggests that the PI3K/AKT pathway is involved in cancer cell response to TTFields, and that inhibition of this pathway may serve as a potential therapeutic target for sensitizing cancer cells to TTFields.

Subsequently, we comprehensively examined all clinical trials that targeted breast cancer patients with PIK3CA mutations. Finally, this review explored the potential of a new treatment for noncoding RNA.

The clinical management of syndromic macrodactyly is well described by consensus guidelines, but isolated macrodactyly also needs pediatricians' attention and warrants a multidisciplinary approach. After reviewing the literature, a diagnostic algorithm for the approach and differential diagnosis of macrodactyly is provided. Phenotypes associated with PI3K/AKT/mTOR pathway mutations (including PIK3CA-related overgrowth spectrum PROS) are described. Late effects, follow-up schedules, and surveillance for cancer are discussed.

A meta-analysis of LC3 and MSK-IMPACT showed that African genetic ancestry was significantly associated with KRAS mutation status and MSI status. This work facilitates precision medicine initiatives by providing insights into the contribution of genetic ancestry to molecular features of colorectal tumors.

We have found that for women with pMBC, the disease is driven by several targetable genetic mutations across subtypes, however our results suggest a reduced prognostic value of TMB for this complex patient group. Taken together, our findings substantiate the value of early genomic profiling to actively identify women that may be eligible for a more individualized treatment scheme.

These findings underscore the critical role of antitumor immunity, particularly CD8+T cell activity, in the efficacy of tipifarnib alone and in combination with alpelisib. The triple combination of tipifarnib, alpelisib, and anti-PD1 treatment showed superior antitumor activity and extended survival in preclinical models, suggesting its potential as a therapeutic strategy for HNSCC patients with HRAS- and PIK3CA-mutation.

Our results revealed gene mutations that are significantly associated with metastatic site selectivity and that frequencies of non-coding mutations at AR chromatin binding sites differ between metastatic sites. Immunotherapeutics are thus far unsuccessful in unselected mCRPC patients. We found a higher TML in liver and visceral metastases compared to bone and lymph node metastases. As immunotherapeutics response is associated with mutational burden, these findings may assist in selecting mCRPC patients for immunotherapy treatment based on organs affected by metastatic disease.

Activating PIK3CA mutations, present in up to 40% of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (Her2-) breast cancer (BC) patients, can be effectively targeted with the alpha isoform-specific PI3K inhibitor Alpelisib...Our findings reveal that aberrant mTORC1 signaling, a common cause of PI3K inhibitor resistance in BC, creates a druggable metabolic vulnerability by suppressing autophagy. Additionally, the combination of 4E-BP1T37/46 phosphorylation and p62 accumulation serves as a biomarker for poor overall survival, suggesting their potential utility in identifying BC patients who may benefit from metabolic therapies.

P1, N=39, Active, not recruiting, National Cancer Institute (NCI) | N=108 --> 39 | Trial completion date: Dec 2024 --> Mar 2026 | Trial primary completion date: Dec 2024 --> Jul 2024

On the other hand, in the BCG-unresponsive group, we found mutations in 44.4% of samples, mainly in TP53 gene. Our findings suggest that a Next-Generation Sequencing (NGS) multigene panel is useful in predicting BCG response in patients with NMIBC.

These findings suggest that somatic gene mutations are closely linked to DRE. Identifying the molecular basis of antiseizure drug resistance is crucial for improving the management of DRE.

Comprehensive immunophenotyping of GAC identifies an inflamed class of tumors that complements previously proposed tumor-based molecular clusters. Such findings may provide the rationale for exploring novel immunotherapeutic approaches for biomarker-enriched populations in order to improve GAC patient's survival.

This study represents the initial description of loss of the SWI/SNF complex expression in PSBA, which is rare and primarily originates in the jejunum and ileum. Further investigations are warranted to elucidate potential targets of PIK3CA inhibitors for dMMR PSBA and ARID1A loss of expression in PSBA.

The concurrent HRAS and PIK3CA mutations suggest potential targeted therapies, emphasizing the importance of a multidisciplinary approach. Further research is needed to establish standardized treatment guidelines for M-AME.

Currently, additional mutations of the pathway, including non-exon 2 mutations in KRAS, mutations in the homologous GTPase NRAS, in kinase BRAF and PIK3CA and other pathway proteins, have been added in the evaluation for responsiveness prediction to cetuximab and panitumumab. In this review, the predictive biomarker landscape for anti-EGFR monoclonal antibody inhibitors in metastatic colorectal cancers with no extended RAS and BRAF mutations will be examined.

HIV-infection status and age appear to be risk factors for higher burden of pathogenic mutations in genes that predispose to cervical cancer. Mutation profiles in PIK3CA and TP53 genes could be biomarkers of cervical cancer progression but more studies are needed.

These findings suggest a potential association between these negative genes especially KRAS mutation and HPD. Therefore, administration of PD-1 blockade monotherapy in this subgroup of patients harboring KRAS mutation should be performed with caution. Further studies are warranted to confirm these results and explore the correlation between genomic mutations and HPD.