bims-necame 2026-05-17 papers

Issue of 2026–05–17
three papers selected by
Grigor Varuzhanyan, UCLA

J Clin Med. 2026 Apr 28. pii: 3353. [Epub ahead of print]15(9):

Pretreatment Lactate Dehydrogenase-to-Albumin Ratio and Clinical Outcomes in Extensive-Stage Small Cell Lung Cancer: A Multicenter Real-World Study.

ONCONET Collaborative Group

Background: Reliable biomarkers that capture tumor-host interactions and predict treatment resistance in extensive-stage small cell lung cancer (SCLC) remain limited. We evaluated the prognostic and predictive value of the pretreatment lactate dehydrogenase-to-albumin ratio (LAR), an integrative biomarker reflecting metabolic activity, systemic inflammation, and host nutritional status. Methods: This multicenter, retrospective cohort study included patients with extensive-stage SCLC treated at five tertiary centers between 2016 and 2024. Pretreatment LAR was calculated using baseline serum lactate dehydrogenase and albumin levels and dichotomized using a Youden index-derived cut-off at the 12-month overall survival (OS) horizon. Time-dependent receiver operating characteristic (ROC) analyses using inverse probability weighting were performed to assess discriminative performance. Survival outcomes were evaluated using Kaplan-Meier estimates and Cox proportional hazards models. Associations with platinum resistance and lack of objective treatment benefit (defined as progressive disease as best response) were examined using logistic regression models. Results: A total of 223 patients were included. Elevated LAR was associated with inferior OS (median, 15.8 vs. 25.2 months; log-rank p < 0.001) and progression-free survival (7.9 vs. 11.5 months; p < 0.001). In multivariable analysis, LAR remained independently associated with OS (HR, 1.43; 95% CI, 1.04-1.95; p = 0.028). LAR demonstrated modest but consistently superior discriminative performance compared with other inflammatory indices for both 12-month OS (area under the curve [AUC], 0.692) and 6-month progression-free survival (PFS) (AUC, 0.646), with statistically significant differences in DeLong comparisons. Higher LAR was independently associated with increased odds of platinum resistance (adjusted odds ratio [aOR], 2.31; 95% CI, 1.41-3.81; p = 0.001) and lack of objective treatment benefit (adjusted OR, 2.04; 95% CI, 1.33-3.14; p = 0.001). Conclusions: Pretreatment LAR is a clinically accessible and biologically integrative biomarker associated with survival and treatment resistance in extensive-stage SCLC. By capturing tumor-host interactions, LAR may support risk stratification and identify patients at increased risk of early treatment failure. Prospective validation is warranted to define its role in biomarker-driven clinical decision-making.

Keywords: LAR; LDH-to-albumin ratio; albumin; extensive stage; immune inflammation; lactate dehydrogenase; prognosis; small-cell lung cancer; survival; treatment failure

DOI: https://doi.org/10.3390/jcm15093353

Cell Rep. 2026 May 12. pii: S2211-1247(26)00408-0. [Epub ahead of print]45(5): 117330

HOXD11-NMDAR signaling drives neuroendocrine prostate cancer and enables potential therapeutic intervention as a target of memantine.

Prostate cancer resistance to androgen deprivation therapy often involves neuroendocrine transformation. Using single-cell RNA sequencing of transgenic adenocarcinoma of the mouse prostate (TRAMP) mice across pathological stages (early adenocarcinoma to late neuroendocrine prostate cancer [NEPC]), we find an early neuroendocrine-initiating cluster marked by elevated HOXD11, conserved in human NEPC. Genetic suppression of HOXD11 blocks neuroendocrine differentiation and restores androgen receptor (AR) signaling. Mechanistically, HOXD11 directly activates FOXA2 and N-methyl-D-aspartate receptor (NMDAR) subunits (GRIN1/GRIN3A), pathways upregulated in NEPC and linked to poor prognosis. Pharmacological NMDAR inhibition with memantine suppresses NEPC progression preclinically. Notably, a preliminary clinical observation in one evaluable patient with chemotherapy-failed NEPC shows radiographic regression of primary and metastatic lesions after memantine treatment. These findings establish HOXD11 as a driver of neuroendocrine transformation and support further investigation of memantine as a candidate therapeutic strategy for NEPC.

Keywords: CP: cancer; CP: neuroscience; HOXD11; NEPC; NMDARs; drug repurposing; lineage plasticity; memantine; neuroendocrine prostate cancer

DOI: https://doi.org/10.1016/j.celrep.2026.117330

Oncol Lett. 2026 Jul;32(1): 275

Multi-omics profiling of pancreatic neuroendocrine tumors: Interplay of genomic instability and the tumor microenvironment (Review).

Yin Wan, Yingnan Zhang, Philip A Philip, Herbert Chen, Bassel El-Rayes, Asfar S Azmi, Yang Shi.

Pancreatic neuroendocrine tumors (PNETs) represent a biologically heterogeneous group of neoplasms shaped by both intrinsic genomic alterations and dynamic interactions with the tumor microenvironment (TME). Conventional analytical approaches offered limited insight into these complex mechanisms. However, the emergence of multi-omics technologies including genomics, transcriptomics, proteomics and spatial single-cell platforms dramatically expanded current understanding of tumor evolution, immune-stromal crosstalk and phenotypic plasticity. In the present review, findings from novel multi-omics studies were integrated to reframe PNET biology through the perspective of TME co-evolution. The present review highlighted how genomic instability serves as a key driver, promoting transcriptomic reprogramming and clonal evolution that subsequently remodels the TME into an immunosuppressive niche rich in cancer-associated fibroblasts and characterized by immune exclusion. The present review further emphasized the novel role of spatial multi-omics in deciphering the spatial heterogeneity of the PNET ecosystem. These insights accelerated the identification of novel biomarkers and revealed novel therapeutic susceptibilities, potentially paving the way for rational combination strategies that target both tumor-intrinsic pathways and microenvironmental constraints. Therefore, the present review proposed that multi-omics profiling provides not only a descriptive landscape but a mechanistic framework for precision oncology, enabling improved patient stratification and biomarker-driven therapeutic interventions in PNETs.

Keywords: genomic instability; immune modulation; multi-omics profiling; pancreatic neuroendocrine tumors; stromal remodeling; tumor microenvironment

DOI: https://doi.org/10.3892/ol.2026.15630