Dysregulated expression of mitochondrial creatine kinase 1B (CKMT1B), a member of the creatine kinase family, has been linked to tumor progression. However, its specific function in lung adenocarcinoma (LUAD) remains unclear. Bioinformatics analyses were performed to evaluate CKMT1B and its upstream transcription factor PITX2 in LUAD. CKMT1B and PITX2 expression levels were determined by quantitative PCR. The functional impact on cell stemness was subsequently evaluated using CCK-8, sphere formation assay, flow cytometry, and western blot. CKMT1B-mediated lipid accumulation was examined via BODIPY staining and measurements of triglyceride and glycerol concentration. The PITX2-CKMT1B interaction was validated through dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays, with the regulatory mechanism further substantiated by functional rescue experiments. CKMT1B was upregulated in LUAD and linked with poor prognosis. Its knockdown suppressed cell proliferation, sphere-forming capacity, and stemness-related protein expression (CD133, Bmi-1, SOX-2). Furthermore, CKMT1B overexpression facilitated lipid accumulation and stemness, effects that were reversible by the lipase inhibitor Orlistat. Mechanistically, PITX2 was identified as an upstream transcription factor of CKMT1B. PITX2 expression was positively correlated with CKMT1B, and high PITX2 expression predicted poor outcomes. In functional rescue experiments, PITX2 knockdown significantly reduced lipid accumulation and stemness, while these effects were partially restored by CKMT1B overexpression. PITX2 promotes lipid accumulation and enhances stemness in LUAD cells by transcriptionally activating CKMT1B, suggesting the PITX2/CKMT1B axis as a potential therapeutic target for LUAD treatment.

KRAS-mutant non-small cell lung cancer (NSCLC) remains a major therapeutic challenge due to the paucity of effective targeted agents. Although covalent KRAS^G12C inhibitorsi such as sotorasib and adagrasib have demonstrated clinical activity, pooled analyses indicate only modest response rates and short progression-free survival, with no effective options for non-G12C subtypes. This highlights the need for novel therapeutic strategies with broader efficacy and improved durability. We evaluated the antiproliferative effects of SP09, a novel benzoin-Schiff base derivative, in KRAS-mutant (A549, H460) and EGFR-mutant (PC9) NSCLC cells, as well as normal lung cells. Cell viability, colony formation, and cell cycle distribution were assessed, and the involvement of the liver kinase B1 (LKB1)/AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR) signaling axis was examined by western blot. SP09 selectively inhibited the proliferation of KRAS-mutant NSCLC cells (IC50 ≈ 29 µM) with minimal toxicity to normal lung cells. Treatment induced G2/M arrest via downregulation of cyclin B1 and upregulation of p21. Mechanistically, SP09 activated the LKB1/AMPK pathway and suppressed mTOR signaling, leading to inhibition of downstream effectors, including P70S6K, S6, and sterol regulatory element-binding protein 1 (SREBP1). SP09 exerts potent and selective antiproliferative effects in KRAS-mutant NSCLC through dual regulation of cell cycle and metabolic signaling pathways. Given the restricted efficacy and rapid resistance associated with current KRAS-targeted therapies, our data highlight SP09 as a promising candidate for further preclinical development with potential translational value in KRAS-driven NSCLC.

Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder associated with central nervous system gliomas, most frequently optic pathway gliomas; however, oligodendrogliomas in the setting of NF1 are exceedingly rare, with no prior documented cases and no established treatment strategies to date. A 53-year-old female with NF1-associated oligodendroglioma experienced multiple recurrences following surgery, radiotherapy, chemotherapy, and targeted therapy. Upon further disease progression, she was treated with a novel combination of thiotepa, bevacizumab, teniposide, and the mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor tunlametinib. After one treatment cycle, the patient achieved a marked reduction in tumor volume, consistent with a complete response (CR). She subsequently completed eight additional cycles of the regimen and has maintained CR. The treatment was well-tolerated, with manageable grade 3 myelosuppression controlled by supportive care. As of June 2025, the patient has achieved a CR with a progression-free survival of 9 months before experiencing disease recurrence. This rare case of NF1-associated oligodendroglioma was managed with thiotepa, bevacizumab, teniposide, and tunlametinib, highlighting the potential of MEK inhibition in NF1-related gliomas.

Osimertinib is an effective strategy for nonsmall-cell lung cancer (NSCLC). However, the acquired resistance neutralizes the efficacy of osimertinib. Herein, we investigated the potential biomarkers of osimertinib-resistant lung cancer. GSE200894 was used to analyze the differentially expressed genes in osimertinib-resistant lung cancer. Sixty-two paired surgical specimens were collected from NSCLC patients with stage I-IV. Gene expression was detected using reverse transcription (RT)-qPCR, western blot, and immunohistochemistry. V-set domain containing T cell activation inhibitor 1 (VTCN1) was overexpressed in osimertinib-resistant lung cancer. High levels of VTCN1 predicted advanced stages and distant metastasis. Moreover, VTCN1 expression was negatively correlated with the purity of CD8+ T cells in lung cancer patients. VTCN1 inhibits the infiltration of effector-memory CD8+ T cells. In addition, overexpressed VTCN1 predicted the exhaustion of CD8+ T cells. VTCN1 inhibits the tumor-killing ability of CD8+ T cells. In summary, VTCN1 is overexpressed in osimertinib-resistant lung cancer patients. High levels of VTCN1 confer to inhibition of CD8+ T cell immunity and immune tolerance in osimertinib-resistant lung cancer patients.

Nuclear protein in testis (NUT) carcinoma is a rare disease characterized by aggressive and rapid progression. There is no standard management of primary pulmonary NUT carcinoma until now, and the median overall survival is only 4.4 months. Here, we describe a case where a 48-year-old woman presented with a dry, lasting half a month, and she was diagnosed with primary pulmonary NUT carcinoma and was given chemotherapy, immunotherapy, antiangiogenesis therapy, and palliative radiotherapy. When secondary tumor progression, she was conducted an organoid drug sensitivity test for better guide therapy. The initial two cycles of first-line and second-line treatments in our patient proved effective and improved the overall survival to more than 8 months. This is the first report of the use of an organoid drug sensitivity test for primary pulmonary NUT carcinoma. It provides a new approach for selecting drugs, particularly when multiple lines of treatment have proven ineffective and the next steps are unclear.

The prognosis of advanced lung large-cell neuroendocrine carcinoma is poor, and the efficacy of targeted therapy is still being explored. A case of RET fusion mutation combined with ALK rearrangement positive advanced lung complex large cell neuroendocrine carcinoma was reported. The patient developed intrapulmonary and bone metastases 8 months after chemotherapy after lung cancer surgery, RET fusion mutations were detected by genetic testing, and intracranial progression occurred 1 year after pilatinib was applied. The comutation of RET and ALK was detected by genetic testing, and the pulmonary progression occurred 2 months after the application of aletinib, after being treated with pilatinib and aletinib, he progressed again in 9 months. We point out that large cell neuroendocrine carcinoma complex patients with RET gene mutation can benefit from targeted therapy, and when drug resistance is accompanied by ALK comutation, the patient can benefit from the treatment of the aletinib combined with pilatinib targeted therapy and the side effect is slight. At the same time, we further explore the resistance mechanism of targeted therapy in lung cancer.

The overexpression of CAV1 in many cancers is linked to chemotherapy resistance, but the exact mechanisms by which CAV1 contributes to resistance in nasopharyngeal carcinoma (NPC) are not fully known. Our research aims to elucidate the potential pathways by which CAV1 contributes to chemotherapy resistance in NPC, providing a basis for developing strategies to overcome resistance. A docetaxel-resistant NPC cell line was established, and CAV1 expression was analyzed in the cell line and the resistant variant using western blot. The sensitivity of the resistant cell line to docetaxel was assessed via cell counting kit-8, colony formation assays, and flow cytometry. Flow cytometry was used to measure lipid reactive oxygen species levels, while kits were employed to determine Fe 2+ and malondialdehyde concentrations. The Ubibrowser database helped identify ubiquitination enzymes that interact with CAV1. The binding relationship between UCHL1 and CAV1 was studied using co-immunoprecipitation and immunofluorescence, which also evaluated the deubiquitination activity of UCHL1 on CAV1. CAV1 is overexpressed in NPC tissues and cells, correlating with adverse patient prognoses. In docetaxel-resistant cells, CAV1 expression is elevated compared to standard NPC cells. Silencing CAV1 increased the sensitivity of these resistant cells to docetaxel. Additionally, treatment with the ferroptosis inducer erastin could counteract the effects of CAV1 overexpression on drug resistance. UCHL1 interacted with CAV1 and inhibited its ubiquitin-mediated degradation pathway. By deubiquitinating CAV1, UCHL1 stabilizes and increases its expression, which inhibits ferroptosis and enhances the resistance of NPC cells to docetaxel.

The objective of this study is to assess the differential expression of ferroptosis suppressor protein 1 (FSP1) in relation to clinical features, platinum resistance, and recurrence in epithelial ovarian cancer (EOC). In addition, the potential significance of FSP1 in EOC as a predictor of platinum resistance and recurrence in EOC was explored. Patients with pathologically confirmed EOC who underwent surgical treatment were included in this analysis. Immunohistochemistry was employed to evaluate FSP1 expression in ovarian tissues, with quantitative analysis performed on the samples. Clinical data were collected during follow-up, and patients were categorized according to platinum resistance and recurrence criteria. Statistical analysis was conducted using SPSS version 27.0. A total of 40 tissue samples from patients with EOC were analyzed, along with 21 samples from benign ovarian tumors and 20 samples from normal ovarian tissues. The expression of FSP1 was significantly higher in the EOC group compared to both benign and normal tissue groups. Meanwhile, the expressions of FSP1 were higher in groups with clinically advanced stages, high-grade carcinoma, presence of cancerous ascites, lymph node metastasis, and in the clear cell EOC group, compared to those with clinically early stages, low-grade carcinoma, absence of cancerous ascites, no lymph node metastasis, and other pathological subtypes. A positive linear correlation was identified between FSP1 expression in EOC tissues and serum levels of CA125 and human epididymis protein 4 at the time of diagnosis. The elevated expression of FSP1 is positively correlated with serum CA125 and human epididymis protein 4 levels at the time of diagnosis, which is a risk factor for EOC drug resistance and recurrence. These findings suggest that FSP1 may serve as a valuable biomarker for predicting platinum resistance and recurrence in patients with EOC.

Immune checkpoint blockage (ICB) therapy has shown minimal effectiveness in anaplastic lymphoma kinase (ALK)-positive nonsmall cell lung cancer (NSCLC) regardless of Programmed death-ligand 1 expression. ALK fusion accompanied by mismatch repair deficiency or microsatellite instability-high (MMRd/MSI-H) and high tumor mutation burden (TMB-H) are extremely rare in NSCLC, and the efficacy of ALK inhibitors or ICB-based therapies is unclear. Here, we report the case of a 60-year-old female patient with metastatic lung adenocarcinoma accompanied by EML4-ALK fusion, TMB-H, MMRd/MSI-H, and pathogenic mutations in TP53, MLH1, and STK11. The patient experienced progression on initial iruplinalkib and subsequent alectinib therapy within 5 months. After the failure of third-line therapy with cisplatin-pemetrexed combined with bevacizumab, she received sintilimab plus anlotinib which led to a progression-free survival of 6.5 months. She received sintilimab combined with albumin-paclitaxel plus carboplatin and achieved partial response after 6 months. She developed adverse events after one cycle of sintilimab plus albumin-paclitaxel treatment. Then she was continued with sintilimab plus anlotinib as a maintenance therapy due to intolerance to chemotherapy. After progression on ICB-based therapy, the patient was treated with lorlatinib and still under follow-up with overall survival of more than 3 years. Our findings highlight the therapeutic potential of ICB-based regimens in patients with MSI-H and ALK-rearranged NSCLC.

We present the case of a young woman diagnosed with chronic myeloid leukemia who began de-novo treatment with nilotinib, which led to increased plasma levels of total bilirubin and QT interval. An evaluation of the genetic profile of uridine diphosphate glucuronosyltransferase was made, as nilotinib inhibits the activity of this enzyme causing hyperbilirubinemia, with higher risk in slow metabolizers, such as those ones with *6/*6 genotype. This type of patient can be identified by genetic profiling, and adjustment in the dose of nilotinib could be made to avoid tyrosine kinase inhibitor switching.