Medical Oncology最新文献

{"title":"Prevalence, detection, and clinical implications of BRAF V600E and NRAS Q61R mutations in multiple myeloma BM-FFPE tissues using digital droplet PCR.","authors":"Niyati S Sharma, K S Nataraj, Bibha Choudhary","doi":"10.1007/s12032-025-03032-5","DOIUrl":"https://doi.org/10.1007/s12032-025-03032-5","url":null,"abstract":"<p><p>Multiple myeloma (MM) exhibits significant genetic heterogeneity with mutations in the MAPK pathway being increasingly recognized as drivers of progression and treatment resistance. This study is the first to employ droplet digital PCR (DD-PCR) on bone marrow formalin-fixed paraffin-embedded (BM-FFPE) tissue to quantify BRAF V600E and NRAS Q61R mutations in MM, and the first such investigation conducted in an Indian MM cohort. Mutations were identified in > 80% of samples. BRAF V600E displayed stage-specific variation, being lowest in intermediate MM and significantly higher in advanced disease (MMII vs MMIII, p = 0.0453). Burden declined after treatment (p = 0.038) and correlated with stage (β = - 36.95, p = 0.0041) and lytic lesions (β = - 25.97, p = 0.0268). NRAS Q61R was enriched in progressive disease (p = 0.02) and showed an upward trend with advancing stage (β = 14.38, p = 0.0686). Higher BRAF and NRAS burdens were associated with reduced 2-year progression-free survival (PFS). We show that DD-PCR applied to BM-FFPE samples is both feasible and informative. However, our study has inherent limitations: DD-PCR measurements can be influenced by sampling biases, droplet variability and FFPE DNA quality. Our single-centre design and small cohort size limit generalizability but demonstrate the potential for DD-PCR to complement sequencing and clinical stratification if validated in larger populations.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"478"},"PeriodicalIF":3.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Caveolae and Rho Kinase: their implication of the senescent cell morphology and the secretion of the SASP in HeLa and A549 cancer cells.","authors":"Yaprak Dilber Şimay Demir, Islam Mohammed Ahmed, Aysun Özdemir, Mustafa Ark","doi":"10.1007/s12032-025-03030-7","DOIUrl":"https://doi.org/10.1007/s12032-025-03030-7","url":null,"abstract":"<p><strong>Purpose: </strong>Caveolae and Rho kinase signaling individually are both remodeled during cellular senescence and influence cell morphology and SASP secretion. However, how this interaction modulates senescent cancer-cell morphology and SASP remains unresolved. We evaluated the possible connection between caveolae and ROCK on the development of senescent cell morphology and the secretion of the SASP.</p><p><strong>Methods: </strong>Senescence was induced in HeLa and A549 cells with ouabain. Caveolin depletion was achieved with methyl-beta-cyclodextrin (MβCD) or Caveolin-1 siRNA applications. Cell morphology was assessed by cell area, volume, and thickness parameters, while SASP secretion was assessed by measuring total protein, IL-6, and VEGF-A in senescent cell secretomes. We also evaluated the effect of caveolae depletion on ROCK expression, activation, and localization.</p><p><strong>Results: </strong>While the caveolae disruption with the preincubation of MβCD did not alter the occurrence of ouabain-induced senescence, it significantly altered cellular morphological features, such as decreased cell area and volume. The amount of ROCK1 and ROCK2 in the membrane fraction of cells was decreased by MβCD preincubation. These findings indicate that there may be a relationship between ROCK and the morphological changes observed in senescent cells as a result of the disruption of the caveolar structure. However, the incubation of MβCD and caveolin-1 knocking down increased the secretory activity of senescent cells. Overall secretion increases with caveolar depletion, indicating that its secretion-enhancing effect is greater than any concomitant decrease that may occur with ROCK inhibition.</p><p><strong>Conclusion: </strong>These data suggest that maintaining the integrity of caveolar structures plays a critical role in mitigating the detrimental effects of SASP released from chemotherapy-induced senescent cells.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"475"},"PeriodicalIF":3.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microsatellite instability and PD-L1 expression in sarcomas: current evidence and clinical perspectives.","authors":"Onyekachi Ewa Ibe, Ilya Ulasov, Svetlana Samoylova, Igor Reshetov","doi":"10.1007/s12032-025-03039-y","DOIUrl":"https://doi.org/10.1007/s12032-025-03039-y","url":null,"abstract":"<p><p>Sarcomas are a diverse group of malignant mesenchymal tumors with complex biology and limited responsiveness to therapies. Several biomarkers yet to be explored as regards sarcoma diagnostics and therapy may be relevant hence the choice of Microsatellite instability (MSI) and programmed death-ligand 1 (PD-L1). Although their expressions are established in various epithelial cancers, their roles in sarcoma remain underexplored. This review provides a comprehensive analysis of the incidence, clinical relevance, and immunotherapeutic implications of MSI and PD-L1 in sarcoma, while also introducing the under-investigated role of lymphovascular invasion (LVI) in modulating immune response. In this study, we found out the rarity but potential therapeutic relevance of MSI-high (MSI-H) status in sarcomas and its correlation with tumor mutational burden (TMB), neoantigen load, and checkpoint blockade sensitivity. Furthermore, this review gave an insight into the immunobiological landscape of sarcomas characterized by concurrent MSI and PD-L1 expression, which, although rare (~ 2-5%), may define a uniquely immunogenic subgroup which may help enable personalized immunotherapy. A key perspective addressed was the interplay between MSI, PD-L1, and LVI which suggested that LVI-positive sarcomas may upregulate PD-L1 as an adaptive immune escape mechanism. Immunohistochemistry, next-generation sequencing data, and recent clinical trials, helped to provide a stratified approach to sarcoma immunotherapy, underscoring the importance of dual biomarker assessment. This review proposes a diagnostic and therapeutic framework that incorporates MSI, IHC, PD-L1, and LVI status to improve prognostication and guide treatment. These novel angles offer fresh direction for future translational research and precision oncology in sarcoma care.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"477"},"PeriodicalIF":3.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The benefits of combining an immunomodulator with a chemotherapy agent in chondrosarcoma-a proof of concept with mifamurtide.","authors":"Rohan Quoniou, Elisa Bortoli, Emmanuel Moreau, Florent Cachin, Emmanuel Chautard, Caroline Peyrode","doi":"10.1007/s12032-025-03038-z","DOIUrl":"https://doi.org/10.1007/s12032-025-03038-z","url":null,"abstract":"<p><p>Tumor-associated macrophages (TAMs) play a critical role in the progression of various cancers, including chondrosarcoma, where they can constitute up to 50% of the tumor mass. In chondrosarcoma, TAMs are predominantly of the M2-like phenotype and are linked to more invasive and higher-grade disease. Despite the challenge of chondrosarcoma's chemo- and radio-resistance due to its slow cell division and unique extracellular matrix, targeting TAMs has emerged as a promising strategy. Therapeutic approaches include inhibiting TAMs recruitment, reprogramming TAMs to a tumoricidal M1 phenotype, and depleting TAMs. Current clinical studies are exploring combinations of TAMs-targeting agents with chemotherapy in many cancers, and some agent like mifamurtide, a TLR4 agonist, is already used with chemotherapy in cancer treatment, for pediatric non-metastatic osteosarcoma. Recent preclinical studies have shown that targeting TAMs in chondrosarcoma can slow tumor growth but no preclinical data shown the relevance of immunomodulator and chemotherapy co-treatment. Our research further evaluates the potential mifamurtide and chemotherapy co-treatment using a 3D co-culture model and a murine xenograft model of chondrosarcoma. Our findings suggest that mifamurtide enhances the chemosensitivity of CH2879/THP-1 spheroids. In the CH2879 xenograft model, its combination with doxorubicin led to improved antitumoral efficacy and a decrease in intermediate-stage tumor-associated macrophages. These results highlight the importance of TAMs in modulating treatment response. This study provides a preclinical proof of concept for the efficacy of combining mifamurtide with doxorubicin in managing chondrosarcoma, highlighting the potential of immunomodulator and chemotherapy co-treatment in improving treatment outcomes.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"476"},"PeriodicalIF":3.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioactive compounds from marine algae in pancreatic cancer therapy: mechanistic insights into fucoidan and phlorotannins: a review.","authors":"N Prabhu, V Rajinikanth, Mathiyazhagan Narayanan","doi":"10.1007/s12032-025-03033-4","DOIUrl":"10.1007/s12032-025-03033-4","url":null,"abstract":"<p><p>Pancreatic cancer is one of the most lethal tumors, marked by a dismal prognosis, few treatment alternatives, and resistance to standard pharmacological interventions. Marine algae are becoming a source of bioactive chemicals with significant anticancer properties. This review examines fucoidan, a sulfated polysaccharide, and phlorotannins, polyphenols exclusive to brown algae, emphasizing their therapeutic effects and molecular mechanisms in pancreatic cancer. Fucoidan inhibits tumor proliferation, promotes apoptosis, regulates immune responses, and prevents metastasis via pathways including PI3K/Akt, MAPK, and NF-κB. Phlorotannins demonstrate antioxidant, anti-inflammatory, and anti-epithelial-mesenchymal transition properties while inhibiting oncogenic signaling. Investigations on synergistic interactions with chemotherapeutics and nanodelivery methods that improve bioavailability are conducted. The discussion encompasses toxicological characteristics, pharmacokinetics, and existing research gaps to tackle translational issues. These discoveries collectively highlight the potential of marine algae chemicals as adjunctive approaches in pancreatic cancer treatment and stress the necessity for additional preclinical and clinical research.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"473"},"PeriodicalIF":3.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antisense LNA GapmeR targeting hsa-piR-33195 induces antiproliferative and apoptotic effects on human acute myeloid leukemia.","authors":"Musarreza Shiri, Mohammadreza Sharifi, Hasan Dianat-Moghadam, Valiollah Mehrzad","doi":"10.1007/s12032-025-03015-6","DOIUrl":"10.1007/s12032-025-03015-6","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is a severe hematologic malignancy caused by the rapid proliferation of myeloid progenitor cells in the bone marrow. Non-coding RNAs, particularly, PIWI-interacting RNAs (piRNAs), play a role in the development of several cancers. Hsa-piR-33195, in particular, may promote AML development since its levels are substantially higher in AML patients. This study explores its anticancer effects and molecular mechanisms in AML cells in vitro. Human AML bone marrow blast cells and KG1 cells were transfected with piR-33195 locked nucleic acid antisense (LNA) GapmeRs 24, 48, and 72 hours after transfection. The transfection efficiency was then assessed using a fluorescent microscope. After that, qRT-PCR was used to measure piR-33195, CASP3, and CASP9. MTT was employed to evaluate the growth and viability of treated cells. Finally, the therapeutic effect of the antisense LNA GapmeRs on cell apoptosis and necrosis was assessed using Annexin V/PI staining. Bioinformatics analyses were conducted to predict the piR-33195 target genes in AML. Findings demonstrated a significant decrease in piR-33195, as well as increased CASP3 and CASP9 expression, in bone marrow samples from AML patients and the KG1 cell line, 24, 48, and 72 hours after transfection with antisense LNA Gamers. Moreover, suppressing piR-33195 markedly reduced cell growth in the transfected cells. Apoptosis and necrosis were significantly elevated in these cells. Bioinformatics identified gene and pathways associated with apoptosis and PI3K-AKT signaling. Inhibiting piR-33195 may be a promising treatment option for AML with fewer adverse effects.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"474"},"PeriodicalIF":3.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor microenvironment response to neoadjuvant therapy in breast cancer: insights from single-cell and spatial omics.","authors":"Qingzhong Wu, Jiawei Yang, Da Zhang, Haowei Xu, Yuhang Yu, Yu Zheng","doi":"10.1007/s12032-025-03028-1","DOIUrl":"10.1007/s12032-025-03028-1","url":null,"abstract":"<p><p>Breast cancer remains a significant public health concern, and neoadjuvant therapy has significantly reconfigured the landscape of its clinical management. The intricate characteristics of the tumor microenvironment (TME) have profound implications for tumor development and therapeutic responses. Thus, understanding the dynamics of the TME during treatment is crucial. Advancements in molecular biology research, such as single-cell analysis and spatial omics technologies, provide valuable tools for investigating the complexities of the breast cancer microenvironment. These innovative approaches facilitate the identification of cellular heterogeneity, spatial interactions, and altered signaling pathways, illuminating the TME's adaptive mechanisms in response to neoadjuvant therapy. In this review, we first elucidate the current status of neoadjuvant therapy in breast cancer. Subsequently, we outline cutting-edge molecular biology research methods and their applications within the breast cancer microenvironment. Finally, we provide an overview of the alterations in the components of the tumor microenvironment during neoadjuvant treatment for breast cancer, focusing on insights gained from single-cell analysis and spatial pathology.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"472"},"PeriodicalIF":3.5,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145054734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting tumor immune evasion: the role of PD-L1 siRNA in advancing cancer immunotherapy.","authors":"Shahad Mohammed Dhiaa Younis, Abdulkareem Shareef, Ashok Kumar Bishoyi, Rami Oweis, H Malathi, Arshdeep Singh, Samir Sahoo, Ashish Singh Chauhan, Hayder Naji Sameer, Ahmed Yaseen, Zainab H Athab, Mohaned Adil","doi":"10.1007/s12032-025-03025-4","DOIUrl":"10.1007/s12032-025-03025-4","url":null,"abstract":"<p><p>Programmed cell death 1 (PD-1) is a CD28/CTLA-4 family member of immune checkpoint inhibitors. A lot of it is also made up of T cells worn out from being around tumors, which weakens the immune system. PD-1 binds to a protein called PD-L1, which stops T cells from fighting cancer. Inhibitors of the PD-1/PD-L1 pathway have changed how cancer is handled and have shown much potential against several types of cancer. However, there have been many accounts of bad things happening with the circulatory system in cancer patients who were being treated with anti-PD-1/PD-L1. To address these issues, it has been essential to develop alternative therapeutic approaches. Using small interfering RNA (siRNAs) to target immune checkpoint molecules can activate immune cells and prevent tumor cells from suppressing these activated immune cells. However, due to the highly charged nucleic acid backbone, making safe and effective tools for delivering these molecules only to tumor cells is a necessary first step toward their future use as medicines. Using secure, biodegradable nanocarriers to give these medicines to their intended locations will improve the treatment. In this study, we discussed the importance of PD-L1 siRNA in treating various types of cancer. Finally, we discussed the problems with this method and examined the new process that can address these issues. This review aims to spark researchers' interest in enhancing PD-L1 siRNA's efficacy against cancer and addressing its therapeutic limitations.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"471"},"PeriodicalIF":3.5,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145054697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-coding RNAs' pivotal importance in modulation of cancer sensitivity to Topotecan: a systematic review.","authors":"Seyed Mostafa Rahimi, Abouzar Bagheri","doi":"10.1007/s12032-025-03029-0","DOIUrl":"10.1007/s12032-025-03029-0","url":null,"abstract":"<p><p>Cancer is one of the leading causes of mortality worldwide. Development of new methods or improving the efficiency of already existing methods is essential in the successful treatment of this disease. Topotecan, a chemotherapeutic drug, has been used to inhibit various cancer types. However, chemotherapy resistance to this drug in cancer has impeded its maximum performance. miRNAs and other non-coding RNAs play crucial roles in regulating this attribute. In this systematic review, we investigated the interaction mechanism between these molecules and Topotecan in the modulation of cancer sensitivity to this agent. This study was carried out according to PRISMA guidelines. PubMed, Scopus, and Web of Science databases were comprehensively searched, using our predefined search terms. Following a selective process based on strategic criteria, eleven studies were included in the analysis. Altered expression levels of non-coding RNAs, especially miRNAs, regulated the sensitivity of cancer cell lines and animal models, directly and indirectly, through affecting cascades of signaling molecules. This impact was recorded in a variety of cancer types, including retinoblastoma, renal cell carcinoma, colorectal cancer, cervical cancer, breast cancer, prostate cancer, and leukemia. The highlighted interactions potentially offer new opportunities for modifying therapeutic intervention utilizing chemotherapeutic agents.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"470"},"PeriodicalIF":3.5,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145054724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying drug targets and evaluating KLK3-targeted inhibitors for prostate cancer using in-silico and in-vitro approaches.","authors":"Imran Zafar, Shaista Shafiq, Adil Jamal, Mohamed Mohany, Muhammad Shafiq, Mohammad Amjad Kamal, Najeeb Ullah Khan","doi":"10.1007/s12032-025-02896-x","DOIUrl":"https://doi.org/10.1007/s12032-025-02896-x","url":null,"abstract":"<p><p>Prostate cancer remains a significant oncological challenge, driven by molecular factors such as KLK3 (kallikrein-related peptidase 3). Text mining of 237,357 PubMed articles identified KLK3 as the most frequently cited protein (10,477 mentions in titles; 162,619 in abstracts), with strong co-mentions of AR, TMPRSS2, and ERG (χ², *p* < 0.001). Structural modeling of KLK3 (PDB: 2ANY) using I-TASSER yielded a high-confidence 3D structure (C-score: 0.73), validated by Ramachandran analysis, with 99.5% of residues falling in favored regions. Phytochemical profiling of Curcuma longa revealed potent bioactive constituents, with leaf extracts showing the highest total phenolic (510.7 ± 0.07 µg/mL) and flavonoid (498.9 ± 0.05 µg/mL) content. LC-MS identified 23 bioactive compounds, which exhibited exceptional binding affinity. Virtual screening of FDA-approved drugs (- 11.8 to - 9.4 kcal/mol), food-derived compounds (- 10.0 to - 9.1 kcal/mol), and natural products (- 11.4 to - 8.8 kcal/mol) revealed significant differences in binding affinities. MK3207 showed the highest binding affinity (- 11.7 kcal/mol), followed by MolPort-039-338-696 (- 11.4 kcal/mol), with key interactions at PHE-110 and THR-167. In-silico docking shows that MK3207 exhibits the strongest binding affinity to KLK3 (- 11.7 kcal/mol), with accuracy validated by an RMSD of 0.195 Å. Pharmacokinetic and drug-likeness evaluation of MK3207 indicated moderate solubility (Log S: - 4.58 to - 5.02), high lipophilicity (consensus log P_o/w: 3.39), favorable drug-likeness (no PAINS/Lipinski violations, bioavailability score: 0.55, synthetic accessibility: 5.21). MD simulations (100 ns) confirmed stable KLK3-ligand binding (final RMSD: 4.3 Å protein, 3.1 Å ligand; average RMSD: 3.99 Å C-α, 3.97 Å backbone, 5.41 Å sidechain). The complex exhibited moderate flexibility (RMSF peaks: 1-4 Å), 28.32% secondary structure, and persistent interactions (hydrophobic: VAL-49, PHE-110; hydrogen bonds: THR-167, SER-213). MM-GBSA analysis revealed strong binding energy (- 75.57 to - 66.36 kcal/mol) and consistent ligand efficiency. This study bridges computational drug discovery and phytochemical analysis, nominating Curcuma longa derivatives and MK3207 as promising KLK3 inhibitors for PC therapy.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"469"},"PeriodicalIF":3.5,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}