The recent study by Liu et al. provided compelling preclinical evidence that lenvatinib enhances the efficacy of combined radiotherapy and PD-L1 blockade by modulating both angiogenesis and antitumor immunity in lung adenocarcinoma. In this correspondence, I discuss the translational implications of these findings and highlight several challenges that should be addressed before clinical implementation. These include the molecular heterogeneity of lung adenocarcinoma, interpatient variability in the temporal dynamics of vascular normalization and immune activation, and the limitations of relying solely on PD-L1 expression for patient selection. I further emphasize the need for biomarker-driven and adaptive clinical trial designs incorporating functional imaging, circulating biomarkers, and immune monitoring to optimize treatment timing and identify patients most likely to benefit from this therapeutic strategy. These considerations may facilitate the successful translation of promising preclinical observations into precision radioimmunotherapy for lung adenocarcinoma.

Platelets, traditionally recognized for their role in hemostasis, are now understood to actively contribute to tumor progression, angiogenesis, and metastasis. Through dynamic bidirectional interactions with cancer cells, platelets undergo measurable alterations in count, mean platelet volume, and molecular cargo, including proteins and mRNAs, supporting their potential utility as liquid biopsy biomarkers for early cancer detection. Within the tumor microenvironment, platelets contribute to immune evasion, support tumor cell intravasation and extravasation, enhance the survival of circulating tumor cells, and promote neovascularization. In addition, they can physically shield malignant cells from immune surveillance, thereby increasing metastatic potential. Although context-specific anti-tumor effects have been reported, the predominant evidence supports a largely pro-tumorigenic and pro-metastatic role for platelets. Elucidating the molecular mechanisms underlying platelet-tumor interactions is therefore essential for improving cancer risk stratification, prognostic evaluation, and therapeutic development. This review summarizes current advances in platelet-derived biomarkers and discusses emerging therapeutic strategies targeting platelet-mediated pathways to suppress metastasis and improve clinical outcomes in cancer patients.

Insulin resistance (IR) is involved in the development, progression, and treatment resistance of cancer. Apart from contributing to obesity and type 2 diabetes, IR leads to hyperinsulinemia, disruption of insulin-like growth factor signaling, chronic inflammation, and metabolic remodeling, which fosters a pro-tumorigenic milieu. These changes stimulate the PI3K-Akt-mTOR, MAPK, JAK-STAT, and NF-κB pathways, which increase proliferation, survival, angiogenesis, immune escape, and metastasis. IR also modifies the tumor microenvironment (TME) and dampens anti-tumor immunity. IGF-1R, IL-6, IL-1β, TNF-α, PD-1, PD-L1, and CTLA-4 monoclonal antibodies could be beneficial by inhibiting inflammatory and oncogenic pathways and reinitiating immune surveillance. Tumor resistance and heterogeneity are significant obstacles. This is a structured narrative review of the molecular connections, antibody treatments, translational obstacles, and future refined approaches in oncology.

DNA double-strand breaks (DSBs) are the most severe DNA damage, and defective repair can lead to apoptosis or malignant transformation. DSBs are mainly repaired by nonhomologous end joining (NHEJ) and homologous recombination (HR), while microhomology-mediated end joining (MMEJ) serves as a backup pathway. Since DNA polymerase theta (Polθ) is essential for MMEJ, this pathway is also named Polθ-mediated end joining. Polθ is barely expressed in normal tissues but overexpressed in many cancers, making it a promising therapeutic target. In recent years, Polθ inhibitors and related therapeutic strategies have emerged rapidly, with clinical trials underway. This review summarizes the structure, function and expression of Polθ in tumorigenesis, highlights synthetic lethal strategies, drug development and clinical translation, and discusses current limitations and future directions for cancer research.

14-3-3 proteins are phosphoserine- and phosphothreonine-binding adaptors that regulate client localization, stability and activity under cellular stress. This narrative review synthesizes stress-specific 14-3-3-client modules in gastric, colorectal, pancreatic, hepatocellular and biliary cancers. Modules were classified as high, moderate, early/context-dependent or background according to mechanistic evidence, functional perturbation, client mapping, treatment-state validation and clinical association. In gastric cancer, G3BP stress granule assembly factor 1 (G3BP1) cooperates with YWHAZ-encoded 14-3-3ζ to retain pro-apoptotic Bax in the cytoplasm. In colorectal cancer, SFN-encoded 14-3-3σ restricts Yin Yang 1 (YY1), sustaining the unfolded protein response and chemotherapy tolerance. In pancreatic cancer, SFN-encoded 14-3-3σ interacts with Yes-associated protein 1 (YAP1) to promote ribonucleotide reductase expression and gemcitabine resistance. In hepatobiliary cancers, SFN-related modules support anoikis resistance but remain context dependent. Clinically relevant units are stress-specific 14-3-3-client complexes rather than total 14-3-3 expression.

Colorectal cancer (CRC) remains a major global health challenge and a leading cause of cancer-related mortality worldwide. Central to its pathogenesis is the dysregulation of interconnected signal transduction networks that govern cellular proliferation, survival, differentiation, apoptosis, and immune modulation. Progressive disruption of these pathways facilitates malignant transformation of the colonic epithelium and underlies disease initiation and progression. In this review, we examine the foundational signaling mechanisms implicated in CRC, with an emphasis on the Wnt/β-catenin, GUCY2C, MAPK/ERK, p53, PI3K/AKT, and SMAD4/TGF-β pathways. We also highlight the genomic and epigenomic hallmarks of CRC to illustrate how genetic and epigenetic alterations contribute to diverse oncogenic processes. Furthermore, we discuss both conventional and emerging precision-based therapeutic strategies aimed at driving mutations in CRC tumorigenesis. By synthesizing advances in signaling biology, this review aims to provide a framework for understanding CRC complexity and to inform the development of more precise and effective therapies.

Pancreatic ductal adenocarcinoma (PDAC) is among the most aggressive human malignancies and has an extremely poor prognosis. Its progression is largely driven by a highly complex and immunosuppressive tumor microenvironment (TME), highlighting the urgent need for a deeper understanding of its molecular mechanisms. Recent advances in single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) have provided unprecedented opportunities to dissect cellular heterogeneity, spatial organization, and gene expression dynamics within the TME. In this review, we summarize the major scRNA-seq and ST technologies and their unique strengths in cancer research and highlight their integrated applications in revealing PDAC heterogeneity, stromal-immune interactions, and mechanisms of therapeutic resistance. We further discuss how these approaches can inform biomarker discovery and guide the development of novel therapeutic strategies. Together, these findings suggest that integrated single-cell and spatial transcriptomics offers transformative potential to advance precision oncology and improve outcomes for patients with pancreatic cancer.