Immune checkpoint inhibitors (ICIs) have improved outcomes in selected patients with metastatic triple-negative breast cancer (mTNBC), particularly those with high programed death-ligand 1 (PD-L1) expression. However, optimal dosing strategies balancing efficacy, toxicity, and cost remain unclear. We report the case of a 34-year-old woman with recurrent mTNBC and high PD-L1 expression (combined positive score, CPS ≥ 60; immunohistochemistry 22C3 pharmDx assay). She achieved durable disease control over 22 months (September 2024 to June 2026) using a combination of gemcitabine maintenance chemotherapy and low-dose intermittent nivolumab (40 mg fixed dose, administered 3-weekly). This de-escalated regimen was adopted due to early treatment toxicity and severe financial constraints. The patient achieved a confirmed partial response by RECIST v1.1 criteria (48% reduction in target lesion size), accompanied by manageable CTCAE Grade 2 hypothyroidism requiring oral levothyroxine replacement. This case illustrates that in biomarker-selected, PD-L1-high mTNBC, combination chemotherapy with low-intensity PD-1 blockade can maintain prolonged antitumor activity. These observations support the working hypothesis of a minimum effective immune dose, warranting prospective evaluation in resource-constrained clinical settings.

Pancreatic ductal adenocarcinoma (PDAC) develops chemoresistance through dynamic cell-state transitions, yet the regulatory network architecture governing drug-tolerant states remains poorly characterised, because static expression snapshots cannot capture how interaction topology evolves along treatment-induced trajectories. We established a 3D PANC-1 tissue model on decellularised porcine intestinal matrix, which reaches patient-like proliferation indices and tissue-niche-specific drug responses, and performed single-cell RNA sequencing across four conditions: control, gemcitabine (GEM), TGF-β1, and their combination. Coupling pseudotime trajectory inference to dynamic protein-protein interaction network analysis, we tracked betweenness centrality continuously across cell-state transitions rather than comparing discrete states. GEM survivors engaged a proliferative programme (E2F1, CDK1, AURKA, TPX2, TOP2A, BIRC5), whereas TGF-β1 induced an independent EMT attractor (SPOCK1, MBOAT2, COL5A1, THBS1, FN1). Where the two converged, an emergent bottleneck appeared: CDK1 betweenness centrality spiked selectively, restrained by CDKN1A (p21) and WEE1, defining an S-phase-persistence state enriched for GEM survivors. Cross-examination in a PDAC atlas of 726,107 cells from 231 patients showed 8.7-fold metastatic enrichment of triple-positive cells. This framework, linking controlled 3D tissue experimentation, single-cell systems analysis and clinical-scale patient data, is applicable to drug resistance across cancer types.

This study reports the synthesis of sharp-edged silver nanocubes (AgNCs) with improved plasmonic characteristics and high structural stability, developed as a surface-enhanced Raman scattering (SERS) substrate for trace-level quantification of anticancer drug gemcitabine (GMC). Multiple techniques were employed to investigate the morphological and structural properties of AgNCs in comparison with conventional silver nanospheres. The polyvinylpyrrolidone (PVP)-stabilized AgNC substrate provided remarkable SERS responses, with diagnostic peaks assigned to the CN stretching mode (1174 cm-1) and CO stretching mode (1196 cm-1), together with prominent CF2 bending (529 cm-1) and ring deformation (460 cm-1) modes. Ultrasensitive detection was achieved in aqueous media over a wide concentration range, with GMC signals experimentally detectable down to 10-12 M. The calculated statistical LOD was 6.2 × 10-11 M. The developed AgNC substrate demonstrates a long shelf life of up to five weeks. Density functional theory (DFT) calculations rationalize the possible analyte-substrate interactions and accompanying binding energies, indicating efficient adsorption through the nitrogen- and oxygen-containing pyrimidine and furanose ring systems, respectively, and supporting charge-transfer contributions that modulate the intensities of key vibrational markers under SERS conditions.

Extranodal NK/T-cell lymphoma (ENKTCL) is a rare aggressive lymphoma whose management is complicated by HIV-1 co-infection due to drug-drug interactions and overlapping toxicities, specifically the convergent hepatorenal and hematological toxicities resulting from the concurrent use of chemotherapeutic regimens and ART. We report a middle-aged HIV-1 positive man (CD4[+] T cells:198/μL, HIV-1 RNA:9.70×10[3] copies/mL) with stage IE ENKTCL nasal type, whose initial nasal congestion was repeatedly misdiagnosed as sinusitis. An integrase strand transfer inhibitor-based (INSTIs) ART was unaffordable, and efavirenz was contraindicated by prior allergy, necessitating continuation of lopinavir/ritonavir-based ART despite its CYP3A4 inhibition. A multidisciplinary team guided concurrent therapy with two full-dose cycles of P-GemOxD (gemcitabine, pegaspargase, oxaliplatin, dexamethasone) followed by consolidative radiotherapy (20 fractions). The patient tolerated treatment without grade ≥ 3 adverse events. Post-therapy PET-CT confirmed complete metabolic response, with HIV-1 RNA undetectable. At 9-month follow-up, remission persisted and CD4[+] T cells rose to 255/μL. This case illustrates that an MDT model offers a practical management framework for delivering full-dose P-GemOxD chemotherapy with non-INSTIs when INSTI-based regimens are not accessible. Our experience provides a reference strategy for managing the therapeutic complexities of concurrent HIV and malignancy.

Intrahepatic cholangiocarcinoma carries a poor prognosis making its management challenging. Histotripsy is a non-invasive, non-ionizing, and non-thermal therapy that mechanically disrupts tumors through acoustic cavitation. We present the case of a 59-year-old man with locally advanced, multifocal, stage II intrahepatic cholangiocarcinoma who achieved a complete pathologic response in the explanted liver after treatment with histotripsy and systemic drug therapy consisting of gemcitabine, cisplatin, durvalumab, and trastuzumab deruxtecan. This case highlights the potential role of noninvasive histotripsy as a bridging therapy to transplantation in selected patients with cholangiocarcinoma.

Gemcitabine (GEM) is a first-line therapeutic option for pancreatic cancer; however, it has low efficacy due to rapidly developed drug resistance and severe dose-limiting myelosuppression. To enhance its therapeutic effect, this study developed a novel peptide-drug conjugate using a CXCR4 antagonistic peptide as the targeting head and gemcitabine as the drug payload, based on the characteristics of pancreatic tumor cells highly expressing CXCR4 that mediates immunosuppression and tumor progression through interaction with its specific ligand CXCL12. The therapeutic effect of the conjugate (P12-GEM) was investigated using pancreatic ductal adenocarcinoma cell lines and an orthotopic pancreatic cancer mouse model. Its myelosuppressive effect was assessed from the perspective of hematological toxicity profiles. The results showed that P12-GEM maintained a cell-killing capability comparable to that of GEM while effectively inhibiting the phosphorylation of Erk and P38, thereby reducing CXCL12-mediated tumor cell migration and adhesion to stromal cells. In a tumor-bearing mouse model, P12-GEM demonstrated superior antitumor efficacy compared to GEM and significantly extended animal survival. Moreover, P12-GEM reduced the proportion of tumor-associated macrophages and increased the infiltration of CD8+ T cells in the tumor microenvironment without reducing platelet and white blood cell counts in the peripheral blood. In summary, P12-GEM possesses dual functions of CXCR4 antagonism and tumor cell killing, contributing to reversal of the immunosuppressive microenvironment and alleviation of myelotoxicity.