Skip to content
2000

Anti-Cancer Agents in Medicinal Chemistry - Volume 26, Issue 2, 2026

Volume 26, Issue 2

Volume 26, Issue 2, 2026

    • Targeting the Lin28/let-7 Axis with Compounds to Regulate Transcriptional Control in Cancer

      https://doi.org/10.2174/0118715206375441250901064006

      Lin28 is a pivotal RNA-binding protein that regulates the biogenesis of let-7 microRNAs, which play a crucial role in the post-transcriptional regulation of oncogenes in cancer. The Lin28/let-7 axis is integral to the regulation of key cellular processes such as proliferation, differentiation, and apoptosis. Lin28 promotes the upregulation of oncogenes, including MYC, RAS, and HMGA2, by inhibiting the maturation of let-7, thereby facilitating tumor initiation, progression, and metastasis. Consequently, targeting the Lin28/let-7 interaction has emerged as a promising therapeutic strategy, particularly for malignancies that lack specific molecular targets. This approach holds potential for downregulating oncogene expression and inhibiting tumor progression. Through a comprehensive review of the literature, this article classifies Lin28/let-7 inhibitors into three categories: CSD/ZKD inhibitors, non-CSD/ZKD inhibitors, and let-7 restorers. CSD/ZKD inhibitors, such as TPEN and KCB3602, function by binding to the CSD or ZKD domains of Lin28, thereby inhibiting its activity. Non-CSD/ZKD inhibitors, including compounds like C1632 and Simvastatin, have been identified as molecules that can reduce Lin28 activity, though their binding sites remain unknown. Let-7 restorers, on the other hand, do not directly target Lin28 but instead work indirectly by modulating the activity of associated molecules, such as Zcchc11 and Zcchc6, thereby promoting the restoration of let-7 expression levels. Notable examples of these include IPA-3 and FPA124. This review summarizes recent advances in the development of Lin28/let-7 inhibitors and their therapeutic potential, providing an important reference for ongoing research on Lin28 inhibitors in cancer therapy.

    • The Function of Poly (U) Binding Splicing Factor 60 (PUF60) in Disease Regulation

      https://doi.org/10.2174/0118715206346843241119105519

      The alternative splicing (AS) of pre-mRNA is an important process in controlling the expression of human genes, which can enrich the diversity of the proteome and regulate gene function. On the contrary, aberrant splicing contributes significantly to numerous human diseases progression, including tumors, neurological diseases, metabolic diseases, infections, and immune diseases. The PUF60, a protein related to RNA splicing, plays critical functions in RNA splicing and gene transcription regulation. In addition, it can achieve synergistic binding with U2AF65 on RNA through interactions in the pyrimidine region, promoting the splicing of introns with weak 3'- splice sites and pyrimidine bundles. Nevertheless, an increasing amount of evidence supports that it shows a significant overexpression pattern in the vast majority of cancer cells and is crucial for embryonic development, indicating that PUF60 may hold the post of a potential therapeutic target for such diseases. These studies have significantly increased our interest in PUF60. Thus, we briefly reviewed the structural domain characteristics of the PUF60, splicing mutants of PUF60, and the roles and functions in human diseases, including various cancers, infections of bacterium and viruses, myositis, and Verheij syndrome. Furthermore, the targeted PUF60 inhibitors and boundedness of the current research were elaborated in the article. The article effectively communicates critical perception and insight, making it a precious resource for those interested in PUF60 research and treatment.

    • Research Progress on Small Molecule Inhibitors of MDM2-p53 Protein-protein Interaction

      https://doi.org/10.2174/0118715206358340250121060830

      The p53 protein, renowned as the “anti-cancer protein,” plays a critical role in regulating the cell cycle, inducing apoptosis, and repairing DNA. Its dysregulation often leads to genomic instability and tumorigenesis. MDM2, a key negative feedback regulator of p53, inhibits both the transcriptional activity and stability of p53, thereby suppressing the anti-cancer effect of p53. With the resolution of the co-crystal structure of the MDM2-p53 complex, using small molecule inhibitors to block their interaction has emerged as a promising cancer treatment strategy. These inhibitors can remove the negative regulation of MDM2 on p53 and allow p53 to function as a “tumor suppressor protein”. Over recent decades, researchers have designed and synthesized small-molecule inhibitors with diverse structures, showing notable anti-cancer efficacy in preclinical studies. Although several inhibitors have entered clinical trials, none have yet been approved. This review comprehensively summarizes the recent advancements in small-molecule inhibitors of MDM2-p53 protein-protein interaction (PPI) according to different types of structural scaffolds, primarily focusing on imidazolines, spirooxindoles, pyrrolidines, pyrrolones, piperidones, purine carboxylic acid derivatives, isoquinolines, pyrazolopyrolidinone analogs, imidazothiazoles, quinolones, and spiroindolines. Additionally, this review focuses on their design, synthesis, and biological evaluation and highlights the structure-activity relationships and ongoing efforts. Despite the progress made, challenges remain. Researchers are exploring strategies to overcome these obstacles in promoting the research on drugs targeting MDM2-p53 PPI with stronger affinity, higher permeability, and a more significant effect.

    • Synthesis and Evaluation of Optical Properties, SHP2 Inhibitory Activity, and Cellular Imaging for Novel 2-Quinolone Derivatives

      https://doi.org/10.2174/0118715206337347250219112715
      Introduction

      Although the development of SHP2 inhibitors has made striking progress, there is no inhibitor in clinical evaluation because of the potential side effects induced by poor drug distribution. Fluorescence imaging technology is widely used in the process of diagnosis and treatment of diseases because of the advantages of rapid imaging and non-destructive detection and might provide a new way to explore the mechanism of drug-target interactions in intact tissue.

      Methods

      A series of 2-quinolone derivatives as fluorescent inhibitors against SHP2 were designed and synthesized, and their spectral properties and biological activities were evaluated in this report. The representative compound had excellent fluorescence properties (: 562 nm, Stokes shift: 170 nm, fluorescence quantum yield: 0.072) and optical stability.

      Results

      Moreover, compound emitted a blue signal in SHP2WT U2OS cells and inhibited the SHP2 enzyme abilities (IC: 20.16 ± 0.95 μM) without the extra combination of suitable fluorophores, linker, or selective-activated molecules.

      Conclusion

      Therefore, we hope that compound could act as a lead to develop novel, convenient, and bifunctional chemical tools to explore the mechanism of drug-target interactions in intact tissue and promote the integrated research progress of diagnosis and treatment of SHP2 related diseases.

    • Talimogene Laherparepvec (T-VEC): Expanding Horizons in Oncolytic Viral Therapy Across Multiple Cancer Types

      https://doi.org/10.2174/0118715206379105250429115604

      Talimogene laherparepvec (T-VEC), the first FDA-approved oncolytic viral therapy, has transformed cancer immunotherapy since its 2015 approval for unresectable melanoma. Engineered from Herpes Simplex Virus type 1 (HSV-1) with deletions in ICP34.5 and ICP47 genes and GM-CSF insertion, T-VEC selectively replicates within the tumor cells, inducing lysis and releasing tumor-derived antigens while stimulating systemic antitumor immunity through dendritic cell activation. Although extensively studied for melanoma, its potential extends beyond this malignancy, with emerging applications in breast cancer, Head and Neck Squamous Cell Carcinoma (HNSCC), and other solid tumors. This review synthesizes T-VEC’s mechanism of action, leveraging dysregulated Ras signalling, impaired interferon pathways in cancer cells, its clinical outcomes, and safety profile across these indications. While prior literature emphasizes melanoma monotherapy and combinations with immune checkpoint inhibitors, less attention has been given to its efficacy in non-melanoma cancers and synergistic potential with chemotherapy or radiation therapy. By exploring recent trials, such as T-VEC with neoadjuvant chemotherapy in triple-negative breast cancer and pembrolizumab in HNSCC, highlighting its versatility. Comparative analysis with other oncolytic viruses like HF-10, oncorine (H101), and measles virus variants positions T-VEC within the virotherapy landscape. Key challenges—systemic delivery, immune clearance, and biomarker development for patient selection—are addressed alongside strategies to enhance immune modulation through novel combinations. This review underscores T-VEC’s expanding role in cancer treatment, offering clinicians’ and researchers’ insights to optimize its therapeutic horizons across diverse malignancies.

    • Analytical Techniques as Indicators of Biomarkers in Proteomics Cancer Diagnosis

      https://doi.org/10.2174/0118715206377391250526054417
      Background

      Cancer is a complex disease marked by changes in the levels and functions of key cellular proteins, including oncogenes and tumor suppressors. Proteomics technology enables the identification of crucial protein targets and signaling pathways involved in cancer cell proliferation and metastasis. Various proteomics techniques have been employed to investigate the molecular mechanisms of cancer, aiding in the confirmation and characterization of heritable disorders.

      Methods

      A comprehensive literature search was conducted using PubMed, ScienceDirect, and Google Scholar with search terms like “Cancer and proteomics” and “Mass spectrometry in oncology,” utilizing Boolean operators for refinement. Selection criteria included peer-reviewed articles in English on MS-based biomarker detection, tumor-specific proteins, and drug resistance markers, excluding non-peer-reviewed works and pre-2000 publications unless foundational. Extracted data focused on MS methodologies, biomarker sensitivity, and clinical applications, particularly advances in detecting low-abundance biomarkers and monitoring treatment response. Methodological quality was assessed using PRISMA, evaluating study design, sample size, reproducibility, and statistical analysis. Ethical approval was not required, but adherence to systematic review guidelines and proper citation were ensured.

      Results

      In this review, we highlighted the advanced analytical technique for cancer diagnosis and management of cancer, and described the objective of novel cancer biomarkers. Mass spectrometry (MS) is transforming cancer diagnostics and personalized medicine by enabling precise biomarker detection and monitoring. Unlike traditional antibody-based methods, MS provides high-throughput, quantitative analysis of tumor-specific proteins in clinical samples like blood and tissue. Advanced MS techniques improve sensitivity, allowing for the identification of low-abundance biomarkers and tumor-associated proteoforms, including post-translational modifications and drug resistance markers. In research, MS-based proteomics supports multi-center biomarker validation studies with standardized protocols, enhancing reproducibility. The integration of proteomic data with genomic and transcriptomic datasets through proteogenomics is refining precision oncology strategies. These advancements are bridging the gap between research and clinical application, making MS a critical tool for early cancer detection, prognosis, and therapy selection.

      Conclusion

      Advancements in technology and analytical techniques have helped to produce more accurate and sensitive cancer-specific biomarkers. These methods are advancing rapidly, and developing high-throughput platforms has yielded great results. However, the substantial variation in protein concentrations makes cancer protein profiling extremely complicated. This shows that more technical developments are required in the future to improve proteome broad screening of cancer cells.

    • GPR65 as a Laryngeal Cancer Risk Gene Identified through Single-Cell Transcriptomics, Mendelian Randomization Analysis, and Experimental Validation

      https://doi.org/10.2174/0118715206414176250905114930
      Introduction

      Laryngeal cancer is a common malignant tumor of the head and neck worldwide. This study aimed to identify potential risk genes, with a particular focus on GPR65, and to investigate its functional mechanism in pathogenesis of laryngeal cancer.

      Materials and Methods

      Comprehensive analyses, including scRNA-seq analysis, genome-wide association study (GWAS), eQTL, and TCGA data, were conducted to identify risk genes for laryngeal cancer and characterize the function of these risk genes. Next, qRT-PCR, immunohistochemistry, cell proliferation, cell migration, and invasion assays were employed to verify the expression of GPR65 and its function in laryngeal squamous cell carcinoma (LSCC) .

      Results

      Single-cell analysis screened 416 highly expressed genes in CD8+ central memory T cells (CD8_CM). Mendelian randomization (MR) analysis identified GPR65 as a crucial gene in the development of laryngeal cancer. GPR65 expression was significantly elevated in the tumor tissues compared to normal tissues, with particularly high levels observed in stage IV HNSCC. , LSCC cell lines (TU686 and Hep-2) exhibited marked upregulation of GPR65 relative to normal epithelial cells, and siRNA-mediated silencing of GPR65 suppressed the proliferation, migration, and invasion of LSCC cells. Furthermore, GPR65 expression showed a positive correlation with immune cell infiltration, particularly CD8+ T cells and M1 macrophages.

      Discussion

      This study identified GPR65 as a potential risk gene for laryngeal cancer through single-cell transcriptomics and MR analyses and provided novel evidence of its involvement in the development of the cancer.

      Conclusion

      The present findings showed that highly expressed GPR65 was a tumor-promoting gene in laryngeal cancer, showing its clinical value as a potential therapeutic target.

    • Jianpi Yiwei Granules for Chemotherapy-Induced Gastrointestinal Reactions: A Randomized Double-Blind Placebo-Controlled Trial

      https://doi.org/10.2174/0118715206427314251002153843
      Introduction

      Chemotherapy-induced gastrointestinal reactions are common in non-small cell lung cancer (NSCLC) patients undergoing carboplatin-based chemotherapy. Jianpi Yiwei granules (JPYW), a traditional Chinese medicine (TCM) formula, can alleviate these symptoms.

      Materials and Methods

      This multi-center, randomized, double-blind, placebo-controlled trial enrolled 136 NSCLC patients scheduled for carboplatin-based chemotherapy. Participants were randomly assigned to the treatment group (JPYW with standard antiemetic drugs) and the control group (placebo with standard antiemetic drugs). The complete control rate of nausea and vomiting was assessed using the Visual Analog Scale (VAS) and patient diaries. Control of anorexia, bloating, constipation, and quality of life was measured using the Functional Living Index-Emesis scale and the Brief Fatigue Inventory (BFI).

      Results

      The primary objective of this study was to assess the efficacy of JPYW in alleviating non-vomiting digestive symptoms, such as nausea and anorexia, in NSCLC patients receiving carboplatin-based chemotherapy. The secondary objective was to evaluate its effect on improving bloating, constipation, quality of life, and safety.

      Discussion

      Previous studies have shown that Chinese herbs, such as ginger, are effective in treating chemotherapy-induced nausea and vomiting (CINV). JPYW, a multi-component TCM formula, contains active compounds from and . JPYW exerts anti-inflammatory and prokinetic effects that can synergistically regulate gastrointestinal functions. Preliminary observations confirmed the safety of JPYW combined with standard chemotherapy.

      Conclusion

      The current findings contribute to the treatment of adverse reactions to tumor chemotherapy and are expected to improve the quality of life for chemotherapy patients.

      China Clinical Trial Registration Center

      (ChiCTR2400092390).

Volumes & issues

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test