KRAS mutation

Among the 41 patients who underwent serial liquid biopsy testing, 25% tested positive after an initial negative result. LB detects therapeutically targetable mutations in 58.5% of PDAC patients and is associated with OS.

This study demonstrates the robust performance of the OFA in identifying clinically relevant genetic alterations in NSCLC. The findings support its clinical utility in precision oncology and provide valuable insights into the genetic landscape of Asian NSCLC, enhancing personalized treatment strategies for lung cancer patients.

Notably, among the nine RDAA-positive NSCLC patients who accepted ALK inhibitor treatment, five achieved objective response including two who experienced complete response (CR). Together, the current study identifies RDAA as an oncogenic driver and proposes an effective targeted therapy strategy for non-mutated NSCLC patients.

A panel of colorectal cancer (CRC) cell lines (n = 10) with varying PI3K and MAPK mutational backgrounds were treated with combinations of 5-Flourouracil (5-FU), radiation, the PI3K inhibitor copanlisib, and/or the MEK inhibitor refametinib, and their effects on proliferation in vitro were measured...Our results suggest that activation of the kinase signalling pathway may modulate PI3K/MEK inhibitor responsiveness in colorectal cancer. Furthermore, the addition of copanlisib to 5-FU chemoradiotherapy resulted in an enhanced anti-proliferative cytotoxic effect compared to 5-FU chemoradiotherapy alone, regardless of the background mutational status, and supports further clinical development of this regimen.

Upfront NGS offers rapid, comprehensive genomic data, guiding tailored therapies and trials in advanced NSCLC. Liquid rebiopsy at progression further refines treatment decisions.

This approach yielded a comprehensive model that distinguishes normal pancreatic tissues from pathological features such as pancreatic intraepithelial neoplasia (PanIN), cancerous regions, hemorrhages, and collagen fibers, as well as a streamlined model designed to rapidly identify normal tissues versus pathologically altered regions, including PanINs. These models offer highly accurate diagnostic tools for the early detection of pancreatic malignancies, thus significantly improving the chance for timely therapeutic intervention against PDAC.

Our study demonstrates that rVAR2 is suitable for detecting ofCS+ cancer-derived sEVs in plasma, thereby providing high efficiency for identifying PDAC patients among a diverse population. These findings suggest that rVAR2-based sEV detection could serve as a powerful diagnostic tool to improve patient survival through early detection.

Inhibition of JOSD2 by RNA interference or its pharmacological inhibitor promotes the polyubiquitination and proteasomal degradation of KRAS mutants, and preferentially impede the growth of KRAS-mutant CRC including patient-derived cells/xenografts/organoids (PDCs/PDXs/PDOs) over that harboring wild-type KRAS. Collectively, this study not only reveals the crucial roles of JOSD2/KRAS positive feedback circuit in KRAS-mutant CRC, but also provides a rationale to target JOSD2 as the promising pan-KRAS-mutation-targeting strategy for the treatment of a broad population of CRC patients with KRAS variant across different mutant types.

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.

Recent advancements in cancer therapy focus on targeting critical mutations and regulatory pathways, particularly KRAS mutations and cyclin-dependent kinases (CDKs), which drive cancer progression. This Patent Highlight showcases the development of novel small-molecule inhibitors for KRAS and CDKs, highlighting their mechanisms of action, critical findings from preclinical studies, and the potential for improving therapeutic outcomes in cancers such as nonsmall cell lung cancer (NSCLC), colorectal, and pancreatic cancers.

Recent preclinical findings indicate farnesyl transferase inhibitors (FTIs) can reduce compensatory mTOR and MAPK pathway activation. Evidence supports combining FTIs with KRAS inhibitors to enhance tumor suppression and delayed resistance.

Study findings highlight the increased use of PD-L1 testing over the years from 2017 to 2020 and recent changes in therapy, with decreased use of chemotherapy and increased use of ICI-chemotherapy combinations during the study in each histomolecular group. Moreover, we observed improvements in survival for patients with metastatic NSCLC relative to historical real-world data.

Patients with advanced lung carcinoids harboring AGAs can derive meaningful benefit from genotype-matched targeted therapies, highlighting potential role for NGS in patients with advanced carcinoids.

We describe the third case of PRNRP diagnosed on fine-needle aspiration biopsy, which enabled several diagnostic studies, including immunocytochemistry and NGS confirmation. With this case we highlight the increasing role of fine-needle aspiration biopsy in the clinical management of a subset of patients with small renal masses.

designed a combinational treatment based on targeting the active-state KRASG12C-mutant variant that characterizes a substantial subset of non-small-cell lung cancer (NSCLC) cases. The authors highlighted that dual targeting with KRASG12C (ON) and mammalian target of rapamycin (mTOR) complex (mTORC)-1-selective inhibition potentially provides a new strategy to overcome drug resistance.

Although first-generation inhibitors of KRAS G12C, such as sotorasib and adagrasib, are highly effective in early-phase studies, resistance invariably develops under selective inhibition pressure and rarely leads to sustained long-term treatment benefits. This review also underscores PROTAC technology's promise to advance precision medicine by providing durable treatment options for KRAS-driven lung cancers. It addresses future directions for optimizing PROTAC efficacy, bioavailability, and patient-specific applications.

Moreover, the degradation caused by 11n manipulated the signaling pathways associated with cell apoptosis, metastasis, and invasion to inhibit the tumor growth both in vitro and in vivo. These findings not only generated a useful tool for exploring the potential of targeting SHP2 degradation but also offered promising candidates to develop novel drugs based on the autophagy mechanism.

The present tumor elucidates the pathogenesis and molecular mechanisms of ovarian MLA and demonstrates that ovarian MLA is an endometriosis-associated neoplasm. Further investigation into the pathogenesis and molecular mechanisms of ovarian MLA may assist in identifying potential therapeutic targets for this rare condition.

MM-H&N shows a significant percentage of WT cases and a limited number of targetable mutations, predominantly involving BRAF/RAS mutations, the latter of which are associated with mucosal lentiginous histology. A subset of patients with consecutive samples demonstrates discordant molecular results, indicating that NGS of all samples may be necessary to determine the most appropriate therapeutic approach.

Patients with KL expression subtype tumors may derive better OS and PFS from abemaciclib versus erlotinib in KRAS-mutated non-small cell lung cancer. These results should be further validated in an independent dataset.

Through a search of the medical literature, we found that there are few reports of CSGB receiving comprehensive treatments and achieving relatively good outcomes. Here, we report a rare case of CSGB with KRAS G12V mutation that achieved survival time of 32 months after receiving a combination of treatments including surgery, chemotherapy, radiotherapy, and immunotherapy, and we conducted a literature review for the disease with the aim of raising awareness of the disease.

During treatment, a total hysterectomy and bilateral salpingo-oophorectomy were performed, and intraoperative intraperitoneal chemotherapy with cisplatin (70 mg) was administered. Additionally, the successful application of KRASG12C inhibitors in other cancer types offers a new approach for the targeted therapy of Krukenberg tumors. Therefore, the present study provides further evidence regarding the genomics of Krukenberg tumors, which may aid in the development of targeted treatment strategies.

P3, N=160, Active, not recruiting, Amgen | Trial completion date: Jun 2025 --> Dec 2025 | Trial primary completion date: Mar 2025 --> Jul 2025

P2, N=125, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Mar 2026

Additional mutations seen in a smaller population of low-grade tumors include USP9X, ARID1A, and PIK3CA, but no specific therapies targeting them have been tested clinically. This review summarizes the clinical, pathologic, and molecular features of low-grade serous ovarian cancer as they are now understood and introduces potential therapeutic targets and new avenues for research.

This approach enabled the determination of 12 NMR2 KRAS-fragment complex structures, providing critical insights into structure-activity relationships to guide ligand optimization. These results demonstrate the streamlined integration of NMR2 into a fragment-based drug discovery pipeline composed of screening, binding characterization, and rapid structural elucidation with or without isotopic labeling.

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.

A comparison of our data with that of the phase III trials KEYNOTE-189 and FLAURA suggests that the improved outcomes are due to the use of CPIs or osimertinib. The clinical trial results are well translated into real-world clinical practice with comparable OS. KRAS patients benefit from CPI treatment like no-mutation patients.

In vivo oral administration of combined Omipalisib/Trametinib treatment was significantly more effective than Omipalisib/SHP099 in reducing implanted tumor growth, and the Omipalisib/Trametinib treatment more effectively reduced tumor progression and prolonged survival in an aggressive genetically engineered mouse model of PDAC than either Omipalisib or Trametinib alone. Altogether, our data support a rationale for a dual treatment strategy targeting both PI3K and MAPK pathways in pancreatic cancers.

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.

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.

Without surgery, the patient received first-line treatment with capecitabine in combination with bevacizumab, which was changed to second-line treatment with TAS-102 in combination with bevacizumab after disease progression, with a progression-free survival of 10 months, achieving a significant survival benefit. Later, due to the patient's poor physical condition, no further medication was administered, and the patient died on 1 September 2022. TAS-102 in combination with bevacizumab for the treatment of elderly patients with metastatic CRC who are ineligible for intensive therapy is a promising treatment option.

Large-scale validation studies are imperative to integrate molecular profiles into clinical practice. Until then, management decisions should be individualized, balancing the thrombotic risks with oncologic considerations.

In conclusion, this study revealed that NEU1 is a key protein in sotorasib cardiotoxicity and that reducing the level of this protein is a critical strategy for the clinical treatment of sotorasib-induced cardiac injury. Schematic representation of a mechanism.

Thanatosomes revealed periodic acid-Schiff reactivity with diastase resistance, fuchsinophilia with Masson's trichrome stain, and dark blue-black color with Mallory's PTAH stain. This is the first report linking thanatosomes in KRAS-mutant pulmonary adenocarcinoma to apoptosis via cleaved caspase-3 staining.

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.

In the phase III CodeBreaK 300 study, sotorasib 960 mg-panitumumab significantly prolonged progression-free survival (PFS) versus investigator's choice (trifluridine/tipiracil or regorafenib) in patients with KRAS G12C-mutated chemorefractory metastatic colorectal cancer (mCRC). No new safety signals were observed. Although not statistically significant, the observed OS HR and ORR along with prior PFS and safety findings support sotorasib 960 mg-panitumumab as a standard of care in patients with chemorefractory KRAS G12C mCRC.

Twelve patients (48%) received adjuvant durvalumab...Among patients with baseline detectable ctDNA levels, the median progression-free survival was 21.3 months and was not reached among patients without baseline ctDNA level detection (hazard ratio, 4.54, P = .04). Prospective liquid biopsy testing among patients treated with definitive chemoradiation therapy identifies driver alterations and markers of radiation response with direct implications for therapy personalization.

The KRAS G12C, KRAS G12A, and KRAS G13D mutations are significantly associated with an increased risk of recurrent VTE. Incorporating these specific KRAS mutations into existing risk scores may enhance their predictive accuracy for recurrent VTE in patients with mCRC.

Molecular docking studies reveal that ZHX2 can form stable complexes with AQP9, involving multiple residues. This research enhances our understanding of the molecular mechanisms regulating the growth and death of KRASG12V CRC cells, paving the way for new therapeutic strategies.

This study highlights the epidemiology of guideline-based targetable alterations in French-Canadian patients with resectable lung adenocarcinoma. The large proportion of patients eligible for targeted therapies will have important impact on oncological practices in the current era of neoadjuvant and perioperative treatments.