TP53 mutation

Key mutational alterations in PSCC, including high TMB and TP53 mutations, have significant implications for early diagnosis and personalized therapies. These findings support the potential use of specific genetic markers to guide targeted therapeutic approaches.

While T790M and C797S mutations are well-described, we also observed a significant number of L718 mutations in osimertinib-treated patients. These data support NGS evaluation of NSCLC that has become resistant to EGFR TKIs.

Immune checkpoints and mechanisms such as PDL1- mediated MHC-1 downregulation, galectins, autophagy, TP53, and P2RX1-negative neutrophils also contribute to immune resistance. Hence, this review summarises the current knowledge regarding the underlying molecular mechanisms of immune resistance in pancreatic cancer, along with several existing molecular therapeutics and approaches to overcome these barriers.

The ERSG signature could be used as a predictor of immunotherapeutic outcomes. The ERSG signature has a predictive value in the prognosis and immunotherapeutic sensitivity in COAD, helping guide the personalized treatment.

Targeting C5AR1 synergistically improves antitumor effect of PD-1 blockade against ATC cell-derived tumors. These findings provide systematic insights into tumor biology and opportunities for drug discovery, accelerating precision therapy for virulent thyroid cancers.

Five patients (7%) developed laboratory tumor lysis syndrome (TLS), including 3 (4%) with clinical TLS. Venetoclax resulted in a high response rate and a prolonged PFS in patients with heavily pretreated LPL/WM.

ANGPTL4 plays a significant role in tumor progression via its positive regulation of EMT and angiogenesis, while possibly harboring a TGF-B dependent role in systemic metastasis. Therefore, ANGPTL4 is a suitable target for future drug development.

In this study, an iron overload model in AML cells via the use of ferric citrate is constructed. In TP53 wild-type AML cells, TFR1 participates in iron-mediated resistance to cytarabine by regulating the entry of iron into the cells. These findings provide a foundation for further exploration of the molecular mechanisms involved in AML resistance to cytarabine.

Among patients with stage IIIC endometrial cancer, POLE mutated tumors exhibited an extremely low prevalence, with no specific molecular profile emerging as the largest molecular subgroup. Despite the significant difference in recurrence-free survival between molecular classes, conventional histopathologic parameters retained crucial prognostic value. Our findings highlight the necessity of integrating molecular classes with pathological characteristics, rather than considering them in isolation as crucial prognostic factors in stage IIIC endometrial cancer.

Our data suggest that molecular classification does not seem useful to tailor the need of nodal dissection in apparent early-stage endometrial cancer. p53 abnormality predicts the risk of having advanced disease at presentation. Further external validation is needed.

Endometrial cancer featured different patterns of recurrence depending on the molecular profile. p53-abnormal molecular profiling was the only independent risk factor for peritoneal relapse, while non-specific molecular profile showed a strong association with distant failures.

Our study identifies known and novel prognostic and predictive biomarker candidates in patients with mCRPC undergoing first-line treatment with enzalutamide or abiraterone acetate. It further provides real-world evidence of the significant potential of genomic profiling of ctDNA to inform treatment in this setting. Clinical trials are warranted to advance the implementation of ctDNA-based biomarkers into clinical practice.

We also summarize recent evidence on how it affects tumor biology, metastasis, and response to therapy. To this extent, we highlight the necessity to include studies of KRAS allelic frequencies in the design of future therapeutic strategies against pancreatic cancer.

Currently, there is no standard treatment or cure for LFS or a germline variant of the TP53 gene. With few exceptions, cancers in people with LFS are treated the same way as cancers in other patients, but research continues into the best way to manage cancers involved in LFS.

PPM1Dms are a prominent genetic feature in MN-BNHL, suggesting a distinct role in its development compared to MN-SC. Further investigation is needed to elucidate the precise contribution of PPM1D and its interaction with other mutations in BNHL-related myeloid neoplasm development and prognosis.

We highlight emerging therapeutic strategies targeting these pathways, including reactivating mutant p53, exploiting synthetic lethality, and addressing immune evasion mechanisms. Furthermore, this review underscores the urgent need for novel, isoform-specific interventions to enhance treatment efficacy and improve patient outcomes in this challenging disease.

This study provides one of the first ethnicity-focused analyses of TP53, WNT, PI3K, TGF-Beta, and RTK/RAS pathway alterations in GC, revealing significant racial/ethnic differences in pathway dysregulation. The findings suggest that TP53 and WNT alterations may play a critical role in GC among H/L patients, while PI3K and TGF-Beta alterations may have greater prognostic significance in NHW patients. These insights emphasize the need for precision medicine approaches that account for genetic heterogeneity and ethnicity-specific pathway alterations to improve cancer care and outcomes for underrepresented populations.

Cytological evaluation and ISRSFC classification are crucial for NSCLC-associated PEs. A multidisciplinary approach integrating cytology, immunohistochemistry, and molecular profiling is essential for optimal management and prognosis.

Furthermore, subcutaneous xenograft experiments in mice demonstrated that ADGRG6 knockdown substantially suppressed the growth of engrafted PAAD tumors. ADGRG6 may serve as a novel prognostic marker and a therapeutic targets for PAAD, playing a crucial role in the proliferation, metastasis, and immune marker regulation of PAAD through elevating protein level of mutated p53.

ANKRD22 exhibited strong binding affinity (ΔG = -7.0 kcal/mol in molecular docking and ∆Gbind = -38.66 ± 6.09 kcal/mol in MDs). Taken together, ANKRD22 could be a promising theragnostic target that might be inhibited by fostamatinib, thereby suppressing PC growth.

The present study suggests a potential association between the presence of the Arg allele at codon 72 within the P53 gene and a heightened susceptibility for developing and metastasizing CRC within the Iranian population. Furthermore, exons 5 to 8 of the P53 gene suggests that mutations localized at these sites may portend a poor prognosis.

Targeted sequencing can help to confirm the diagnosis of AEL especially in dilute marrows. The online version contains supplementary material available at 10.1007/s12288-024-01826-7.

Strikingly, however, when we treated pregnant females with the anti-inflammatory drug supformin (LCC-12), we observed a fivefold increase in the proportion of viable Trp53YC/YC weaned females in their progeny. Together, these data suggest that the p53Y217C mutation not only abrogates wildtype p53 functions but also promotes inflammation, with oncogenic effects in males and teratogenic effects in females.

© 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

While the haematoxylin and eosin stain remains the most powerful tool, p53 IHC is a valuable adjunct for determining and diagnosing dysplasia. Although p53 is helpful in predicting the risk of dysplasia in non-dysplastic Barrett's oesophagus, its sensitivity is low, limiting its routine use in this context.

LFS is associated with a heightened risk of rapid progression to invasive carcinomas due to TP53 variants. Therefore, earlier initiation of colonoscopy screening may be necessary for patients with LFS.

In contrast, most UPS occurring in young adults genomically parallel their older adults' counterparts. P-UPS and YA-UPS exhibited a better disease-specific and progression-free survival, compared to A-UPS.

The mass enlarged by 4 cm raising concerns about potential complications, including hemorrhage, which led to hepatic segmental resection. Histopathological examination revealed predominantly BAF features with focal areas that showed malignant cholangiocarcinoma characteristics.

Most patients were treated with immunomodulating therapy, two received methotrexate, three received multiagent chemotherapy and one underwent hematopoietic stem cell transplant...Our results showed that patients with persistent/progressive systemic HV-LPD have a poor prognosis and do not respond well to chemotherapy. The mutation spectrum bore some resemblance to extranodal NK/T lymphomas but also had notable differences.

Additionally, silencing either p53R172H or p53R270H individually leads to marked increases in lysophospholipid levels. These findings offer new insights into the lipidome reprogramming induced by the loss of mutant p53 and underscore changes in lipid storage as a potential key molecular mechanism in PDAC pathogenesis.

No abstract available

Biomarker analysis identified PD-L1 expression, TP53 mutation status, and CD8+ T cell density as potential predictive markers. Therefore, neoadjuvant TNT shows promising anti-tumor activity and acceptable toxicity.

The analysis of mutation profiles and survival outcomes revealed that the transformation subtype affects prognosis. Additionally, the time taken to undergo transformation is critical for patient outcomes.

This study identified several factors significantly associated with worse response to EGFR-TKIs in NSCLC patients with EGFR L858R mutation and respective independent predictive factors for PFS and OS. These findings could enable personalized therapeutic efficacy assessment to facilitate clinical decision-making for EGFR L858R-mutant NSCLC patients treated with EGFR-TKIs.

This study identifies ASNS and ZNF419 as novel prognostic biomarkers in PCa, contributing to improved risk stratification and personalized treatment strategies. Further investigation into their functional roles may provide insights into therapeutic targets for PCa management.

ER status improves prognostic stratification within the NSMP subgroup in ENOC, with ER-negative tumors associated with a worse prognosis. These findings may lead to more personalized treatment strategies for ENOC.

This study constructed a multidimensional strategy that might indicate the prognosis of BTC immunotherapy, enabling the recognition of BTC patients who would benefit from immunotherapy, thereby guiding personalized clinical decision-making.

Furthermore, HDAC6 maintains the activation of the ATF6 branch of the unfolded protein response (UPR), enhancing the ability of mutp53 cells to resist ER stress, as ATF6 supports cellular adaptation to misfolded proteins and stressful conditions. Since HDAC6 is central to this enhanced stress resistance and DNA repair, targeting it could disrupt these protective mechanisms, increasing the vulnerability of mutp53 cancer cells to ER stress and inhibiting cancer progression.

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.

HER2 amplification was found in 10% of advanced BTC and was not identified as an independent prognostic factor for OS. Patients with HER2-amplified BTC derive significant benefit from HER2-targeted therapy.

This study integrates gene expression data from newly diagnosed AML patients, revealing the heterogeneity of pyroptosis patterns within the population. It highlights the potential links between distinct pyroptosis patterns, the immune microenvironment, various cell death pathways, leukemia stemness, and genomic alterations, offering novel biomarkers and therapeutic targets for risk stratification and immunomodulatory interventions in AML.

A library of potent WEE1 kinase inhibitors was synthesized based on the discontinued frontrunner clinical candidate AZD1775 (1), many of which were more selective for WEE1 over an undesirable off-target of 1, the kinase PLK1. When tested against patient-derived organoids (PDOs) grown from TP53-mutated colorectal cancer (CRC) peritoneal metastases, 34 (IC50 value of 62 nM) exhibited stronger efficacy than 1 (IC50 value of 120 nM) and the best-in-class clinical candidate ZN-c3 (IC50 value of 127 nM). Against primary CRC PDOs with TP53-WT, 34 significantly enhanced DNA damage, replication stress and apoptosis compared to 1, as well as demonstrated high selectivity over patient-matched normal healthy colon PDOs, highlighting a potential therapeutic window for cancer treatment. Overall, this investigation provides critical insight into several potent WEE1 inhibitors that exhibited exceptional efficacy against CRC PDOs and is the first to utilize a PDO platform to assess their effect on healthy and malignant cell viability.