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Search Results (974)

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Keywords = epidermal growth factor inhibitor

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17 pages, 2353 KiB  
Article
Repurposing a Lipid-Lowering Agent to Inhibit TNBC Growth Through Cell Cycle Arrest
by Yi-Chiang Hsu, Kuan-Ting Lee, Sung-Nan Pei, Kun-Ming Rau and Tai-Hsin Tsai
Curr. Issues Mol. Biol. 2025, 47(8), 622; https://doi.org/10.3390/cimb47080622 - 5 Aug 2025
Abstract
Triple-negative breast cancer (TNBC) is a highly aggressive and therapeutically challenging subtype of breast cancer due to its lack of estrogen receptors, progesterone receptors, and HER2 (Human epidermal growth factor receptor 2) expression, which severely limits available treatment options. Recently, Simvastatin—a widely used [...] Read more.
Triple-negative breast cancer (TNBC) is a highly aggressive and therapeutically challenging subtype of breast cancer due to its lack of estrogen receptors, progesterone receptors, and HER2 (Human epidermal growth factor receptor 2) expression, which severely limits available treatment options. Recently, Simvastatin—a widely used HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitor for hyperlipidemia—has garnered interest for its potential anticancer effects. This study investigates the therapeutic potential of Simvastatin in triple-negative breast cancer (TNBC). The results demonstrate that Simvastatin significantly inhibits the proliferation of TNBC cells, particularly MDA-MB-231, in a dose- and time-dependent manner. Mechanistically, Simvastatin primarily induces G1 phase cell cycle arrest to exert its antiproliferative effects, with no significant evidence of apoptosis or necrosis. These findings support the potential repositioning of Simvastatin as a therapeutic agent to suppress TNBC cell growth. Further analysis shows that Simvastatin downregulates cyclin-dependent kinase 4 (CDK4), a key regulator of the G1/S cell cycle transition and a known marker of poor prognosis in breast cancer. These findings highlight a novel, apoptosis-independent mechanism of Simvastatin’s anticancer action in TNBC. Importantly, given that many breast cancer patients also suffer from hyperlipidemia, Simvastatin offers dual therapeutic benefits—managing both lipid metabolism and tumor cell proliferation. Thus, Simvastatin holds promise as an adjunctive therapy in the treatment of TNBC and warrants further clinical investigation. Full article
(This article belongs to the Section Molecular Medicine)
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19 pages, 4313 KiB  
Article
Integrating Clinical and Imaging Markers for Survival Prediction in Advanced NSCLC Treated with EGFR-TKIs
by Thanika Ketpueak, Phumiphat Losuriya, Thanat Kanthawang, Pakorn Prakaikietikul, Lalita Lumkul, Phichayut Phinyo and Pattraporn Tajarernmuang
Cancers 2025, 17(15), 2565; https://doi.org/10.3390/cancers17152565 - 3 Aug 2025
Viewed by 181
Abstract
Background: Epidermal growth factor receptor (EGFR) mutations are presented in approximately 50% of East Asian populations with advanced non-small cell lung cancer (NSCLC). While EGFR-tyrosine kinase inhibitors (TKIs) are the standard treatment, patient outcomes are also influenced by host-related factors. This study aimed [...] Read more.
Background: Epidermal growth factor receptor (EGFR) mutations are presented in approximately 50% of East Asian populations with advanced non-small cell lung cancer (NSCLC). While EGFR-tyrosine kinase inhibitors (TKIs) are the standard treatment, patient outcomes are also influenced by host-related factors. This study aimed to investigate clinical and radiological factors associated with early mortality and develop a prognostic prediction model in advanced EGFR-mutated NSCLC. Methods: A retrospective cohort was conducted in patients with EGFR-mutated NSCLC treated with first line EGFR-TKIs from January 2012 to October 2022 at Chiang Mai University Hospital. Clinical data and radiologic findings at the initiation of treatment were analyzed. A multivariable flexible parametric survival model was used to determine the predictors of death at 18 months. The predicted survival probabilities at 6, 12, and 18 months were estimated, and the model performance was evaluated. Results: Among 189 patients, 84 (44.4%) died within 18 months. Significant predictors of mortality included body mass index <18.5 or ≥23, bone metastasis, neutrophil-to-lymphocyte ratio ≥ 5, albumin-to-globulin ratio < 1, and mean pulmonary artery diameter ≥ 29 mm. The model demonstrated good performance (Harrell’s C-statistic = 0.72; 95% CI: 0.66–0.78). Based on bootstrap internal validation, the optimism-corrected Harrell’s C-statistic was 0.71 (95% CI: 0.71–0.71), derived from an apparent C-statistic of 0.75 (95% CI: 0.74–0.75) and an estimated optimism of 0.04 (95% CI: 0.03–0.04). Estimated 18-month survival ranged from 87.1% in those without risk factors to 2.1% in those with all predictors. A web-based tool was developed for clinical use. Conclusions: The prognostic model developed from fundamental clinical and radiologic parameters demonstrated promising utility in predicting 18-month mortality in patients with advanced EGFR-mutated NSCLC receiving first-line EGFR-TKI therapy. Full article
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22 pages, 8682 KiB  
Article
Predicting EGFRL858R/T790M/C797S Inhibitory Effect of Osimertinib Derivatives by Mixed Kernel SVM Enhanced with CLPSO
by Shaokang Li, Wenzhe Dong and Aili Qu
Pharmaceuticals 2025, 18(8), 1092; https://doi.org/10.3390/ph18081092 - 23 Jul 2025
Viewed by 229
Abstract
Background/Objectives: The resistance mutations EGFRL858R/T790M/C797S in epidermal growth factor receptor (EGFR) are key factors in the reduced efficacy of Osimertinib. Predicting the inhibitory effects of Osimertinib derivatives against these mutations is crucial for the development of more effective inhibitors. This study aims [...] Read more.
Background/Objectives: The resistance mutations EGFRL858R/T790M/C797S in epidermal growth factor receptor (EGFR) are key factors in the reduced efficacy of Osimertinib. Predicting the inhibitory effects of Osimertinib derivatives against these mutations is crucial for the development of more effective inhibitors. This study aims to predict the inhibitory effects of Osimertinib derivatives against EGFRL858R/T790M/C797S mutations. Methods: Six models were established using heuristic method (HM), random forest (RF), gene expression programming (GEP), gradient boosting decision tree (GBDT), polynomial kernel function support vector machine (SVM), and mixed kernel function SVM (MIX-SVM). The descriptors for these models were selected by the heuristic method or XGBoost. Comprehensive learning particle swarm optimizer was adopted to optimize hyperparameters. Additionally, the internal and external validation were performed by leave-one-out cross-validation (QLOO2), 5-fold cross validation (Q5fold2) and concordance correlation coefficient (CCC), QF12, and QF22. The properties of novel EGFR inhibitors were explored through molecular docking analysis. Results: The model established by MIX-SVM whose kernel function is a convex combination of three regular kernel functions is best: R2 and RMSE for training set and test set are 0.9445, 0.1659 and 0.9490, 0.1814, respectively; QLOO2, Q5fold2, CCC, QF12, and QF22 are 0.9107, 0.8621, 0.9835, 0.9689, and 0.9680. Based on these results, the IC50 values of 162 newly designed compounds were predicted using the HM model, and the top four candidates with the most favorable physicochemical properties were subsequently validated through PEA. Conclusions: The MIX-SVM method will provide useful guidance for the design and screening of novel EGFRL858R/T790M/C797S inhibitors. Full article
(This article belongs to the Special Issue QSAR and Chemoinformatics in Drug Design and Discovery)
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11 pages, 1453 KiB  
Case Report
Exosome-Based Therapy for Skin Complications in Oncology Patients Treated with EGFR Inhibitors: A Case Report Highlighting the Need for Coordinated Dermato-Oncologic Care
by Lidia Majewska, Karolina Dorosz and Jacek Kijowski
Pharmaceuticals 2025, 18(8), 1090; https://doi.org/10.3390/ph18081090 - 23 Jul 2025
Cited by 1 | Viewed by 315
Abstract
Patients undergoing epidermal growth factor receptor inhibitor (EGFRI) therapy frequently experience dermatologic side effects, notably papulopustular rash, which impacts 50–90% of recipients. This rash typically appears on the face, chest, and back within weeks of treatment, resembling acne but stemming from distinct pathophysiological [...] Read more.
Patients undergoing epidermal growth factor receptor inhibitor (EGFRI) therapy frequently experience dermatologic side effects, notably papulopustular rash, which impacts 50–90% of recipients. This rash typically appears on the face, chest, and back within weeks of treatment, resembling acne but stemming from distinct pathophysiological mechanisms, causing significant discomfort and reduced quality of life. Prophylactic measures and symptom-based treatment are recommended, emphasizing patient education, topical agents, and systemic therapies for severe cases. A 41-year-old female with advanced colonic mucinous adenocarcinoma developed severe acneiform rash and pruritus during EGFRI therapy with panitumumab. Initial standard treatment with oral doxycycline was discontinued after two days due to severe gastrointestinal intolerance characterized by intense nausea and dyspepsia. With limited access to dermatological consultation, treatment with rose stem cell-derived exosomes (RSCEs) provided rapid symptom relief. Significant improvement was observed within 24 h, with complete resolution of pruritus and substantial reduction in inflammatory lesions within 72 h. RSCEs demonstrate anti-inflammatory effects through the modulation of pro-inflammatory cytokines including interleukin-6, interleukin-1β, and tumor necrosis factor-α, while promoting fibroblast proliferation and collagen synthesis enhancement. They may represent a possible alternative to corticosteroids, avoiding associated side effects such as skin atrophy, delayed wound healing, and local immunosuppression. This case underscores the potential of innovative treatments like RSCEs in managing EGFRI-induced skin complications when standard therapies are not tolerated, particularly in healthcare systems with limited dermato-oncological resources. Full article
(This article belongs to the Section Biopharmaceuticals)
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21 pages, 810 KiB  
Review
Molecular Crosstalk and Therapeutic Synergy: Tyrosine Kinase Inhibitors and Cannabidiol in Oral Cancer Treatment
by Zainab Saad Ghafil AlRaheem, Thao T. Le, Ali Seyfoddin and Yan Li
Curr. Issues Mol. Biol. 2025, 47(8), 584; https://doi.org/10.3390/cimb47080584 - 23 Jul 2025
Viewed by 304
Abstract
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, with oral squamous cell carcinoma (OSCC) accounting for a significant portion of cases. Despite advancements in treatment, only modest gains have been made in HNSCC/OSCC control. Epidermal growth factor [...] Read more.
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, with oral squamous cell carcinoma (OSCC) accounting for a significant portion of cases. Despite advancements in treatment, only modest gains have been made in HNSCC/OSCC control. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have emerged as targeted therapies for OSCC in clinical trials. However, their clinical efficacy remains a challenge. Cannabidiol (CBD), a non-psychoactive phytochemical from cannabis, has demonstrated anticancer and immunomodulatory properties. CBD induces apoptosis and autophagy and modulates signaling pathways often dysregulated in HNSCC. This review summarizes the molecular mechanisms of EGFR-TKIs and CBD and their clinical insights and further discusses potential implications of combination targeted therapies. Full article
(This article belongs to the Special Issue Novel Drugs and Natural Products Discovery)
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23 pages, 2993 KiB  
Review
Recent Research Advances in HER2-Positive Breast Cancer Concerning Targeted Therapy Drugs
by Junmin Li, Xue Li, Ruixin Fu, Yakun Fang, Chunmei Zhang, Bingbing Ma, Yanan Ding, Chuanxin Shi and Qingfeng Zhou
Molecules 2025, 30(14), 3026; https://doi.org/10.3390/molecules30143026 - 18 Jul 2025
Viewed by 700
Abstract
Breast cancer is one of the most common malignant tumors among women, which seriously threatens women’s health. Human epidermal growth factor receptor 2 (HER2)-positive breast cancer, characterized by poor prognosis, is an aggressive phenotype accounting for 15–20% of all kinds of breast cancers. [...] Read more.
Breast cancer is one of the most common malignant tumors among women, which seriously threatens women’s health. Human epidermal growth factor receptor 2 (HER2)-positive breast cancer, characterized by poor prognosis, is an aggressive phenotype accounting for 15–20% of all kinds of breast cancers. Therefore, it has attracted great interest among researchers in discovering targeted therapy drugs countering HER2, and they have been considered as the pivotal therapeutic regimen for HER2-positive breast cancer patients. Nowadays, large progress has been achieved in HER2-targeted drugs, and this review categorizes them into four types according to the drug action mode, including monoclonal antibodies (mAbs), tyrosine kinase inhibitors (TKIs), antibody-drug conjugates (ADCs), and bispecific antibodies (bsAbs). The progress of HER2-targeted drugs reflects the discovery of drug targets, the screening of drug compounds, and the modification of antibodies, which offer diverse medical options and better therapeutic benefits for individual patients. In detail, we focus on the indication, administration, efficacy, strengths, and challenges of HER2-targeted drugs, concerning approved drugs and clinical trials. This review aims to provide significant references for the targeted therapeutic regimen and a more precise treatment strategy for HER2-positive breast cancer. Full article
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31 pages, 4404 KiB  
Review
Recent Advances in the Use of Ganoderma lucidum and Coriolus versicolor Mushrooms to Enhance the Anticancer Efficacy of EGFR-Targeted Drugs in Lung Cancer
by Hang Zhang, Longling Wang, Yuet Wa Chan, William C. Cho, Zhong Zuo and Kenneth K. W. To
Pharmaceutics 2025, 17(7), 917; https://doi.org/10.3390/pharmaceutics17070917 - 15 Jul 2025
Viewed by 688
Abstract
Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) is the major subtype, accounting for more than 85% of all lung cancer cases. Recent advances in precision oncology have allowed NSCLC patients bearing specific oncogenic epidermal growth [...] Read more.
Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) is the major subtype, accounting for more than 85% of all lung cancer cases. Recent advances in precision oncology have allowed NSCLC patients bearing specific oncogenic epidermal growth factor receptor (EGFR) mutations to respond well to EGFR tyrosine kinase inhibitors (TKIs). Due to the high EGFR mutation frequency (up to more than 50%) observed particularly in Asian NSCLC patients, EGFR-TKIs have produced unprecedented clinical responses. Depending on their binding interactions with EGFRs, EGFR-TKIs are classified as reversible (first-generation: gefitinib and erlotinib) or irreversible inhibitors (second-generation: afatinib and dacomitinib; third-generation: osimertinib). While the discovery of osimertinib represents a breakthrough in the treatment of NSCLC, most patients eventually relapse and develop drug resistance. Novel strategies to overcome osimertinib resistance are urgently needed. In Asian countries, the concomitant use of Western medicine and traditional Chinese medicine (TCM) is very common. Ganoderma lucidum (Lingzhi) and Coriolus versicolor (Yunzhi) are popular TCMs that are widely consumed by cancer patients to enhance anticancer efficacy and alleviate the side effects associated with cancer therapy. The bioactive polysaccharides and triterpenes in these medicinal mushrooms are believed to contribute to their anticancer and immunomodulating effects. This review presents the latest update on the beneficial combination of Lingzhi/Yunzhi and EGFR-TKIs to overcome drug resistance. The effects of Lingzhi/Yunzhi on various oncogenic signaling pathways and anticancer immunity, as well as their potential to overcome EGFR-TKI resistance, are highlighted. The potential risk of herb–drug interactions could become critical when cancer patients take Lingzhi/Yunzhi as adjuvants during cancer therapy. The involvement of drug transporters and cytochrome P450 enzymes in these herb–drug interactions is summarized. Finally, we also discuss the opportunities and future prospects regarding the combined use of Lingzhi/Yunzhi and EGFR-TKIs in cancer patients. Full article
(This article belongs to the Special Issue Combination Therapy Approaches for Cancer Treatment)
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26 pages, 1735 KiB  
Perspective
Optimizing Adjuvant Care in Early Breast Cancer: Multidisciplinary Strategies and Innovative Models from Canadian Centers
by Angela Chan, Nancy Nixon, Muna Al-Khaifi, Alain Bestavros, Christine Blyth, Winson Y. Cheung, Caroline Hamm, Thomas Joly-Mischlich, Mita Manna, Tom McFarlane, Laura V. Minard, Sarah Naujokaitis, Christine Peragine, Cindy Railton and Scott Edwards
Curr. Oncol. 2025, 32(7), 402; https://doi.org/10.3390/curroncol32070402 - 14 Jul 2025
Viewed by 647
Abstract
The adjuvant treatment landscape for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) early breast cancer (EBC) is rapidly evolving, with a diverse range of therapeutic options—including endocrine therapies, bisphosphonates, ovarian function suppression, olaparib, CDK4/6 inhibitors, and emerging agents such as [...] Read more.
The adjuvant treatment landscape for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) early breast cancer (EBC) is rapidly evolving, with a diverse range of therapeutic options—including endocrine therapies, bisphosphonates, ovarian function suppression, olaparib, CDK4/6 inhibitors, and emerging agents such as immunotherapy. While these advances have markedly improved patient outcomes, they also introduce challenges related to implementation, monitoring, and resource allocation. Notably, therapies like CDK4/6 inhibitors require particularly close monitoring, creating logistical and capacity challenges for medical oncologists, whose workloads are already stretched due to rising cancer incidence and treatment complexities. These challenges underscore the need for innovative care delivery solutions to ensure patients with EBC continue to receive optimal care. This paper offers a comprehensive guide—a playbook—of multidisciplinary-team-based care models designed to optimize adjuvant treatment delivery in EBC. Drawing on real-world evidence and successful applications across Canadian centers, we explore models led by nurses, nurse practitioners (NPs), general practitioners in oncology (GPO), and pharmacists. Each model leverages the unique expertise of its team to manage treatment toxicities, facilitate adherence, and enhance patient education, thereby promoting effective and sustainable care delivery. Importantly, these models are not intended to compete with one another, but rather to serve as a flexible recipe book from which breast cancer care teams can draw strategies tailored to their local resources and patient needs. By detailing implementation strategies, benefits, and challenges—in many instances supported by quantitative metrics and economic evaluations—this work aims to inspire care teams nationwide to optimize the adjuvant management of patients with HR+, HER2– EBC. Full article
(This article belongs to the Section Breast Cancer)
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21 pages, 3752 KiB  
Article
Virulence and Antibiotic Resistance Profiles of Staphylococcus aureus Isolated from Epidermal Growth Factor Receptor Inhibitors-Associated Skin Lesions
by Mara-Mădălina Mihai, Iuliana Anghelescu, Alina Maria Holban, Irina Gheorghe-Barbu, Mariana-Carmen Chifiriuc, Lia-Mara Dițu, Cornelia-Ioana Ilie, Dan Anghelescu and Beatrice Bălăceanu-Gurău
Int. J. Mol. Sci. 2025, 26(14), 6595; https://doi.org/10.3390/ijms26146595 - 9 Jul 2025
Viewed by 401
Abstract
Cutaneous adverse reactions (CARs) are common complications of epidermal growth factor receptor (EGFR) inhibitor therapy, with papulopustular eruptions and paronychia being the most frequent. Growing scientific evidence implies that Staphylococcus aureus is involved in the pathogenesis of these reactions. This observational prospective study [...] Read more.
Cutaneous adverse reactions (CARs) are common complications of epidermal growth factor receptor (EGFR) inhibitor therapy, with papulopustular eruptions and paronychia being the most frequent. Growing scientific evidence implies that Staphylococcus aureus is involved in the pathogenesis of these reactions. This observational prospective study characterized 42 S. aureus strains isolated from CARs, analyzing antibiotic resistance, biofilm formation, soluble virulence factors, and virulence/resistance genes using multiplex polymerase chain reaction (PCR). S. aureus was identified in 90% of lesions; in 33% of cases, nasal and skin isolates were genetically identical. High resistance rates were noted for penicillins (85%) and tetracyclines (57%), while all strains remained susceptible to fluoroquinolones, vancomycin, and rifampicin. All isolates formed biofilms, and DNase/esculinase production significantly correlated with CAR severity. An enzymatic score based on these markers was associated with an 18-fold increased risk of severe reactions. Genotypically, clfA and clfB were prevalent (85.7%), while exotoxin genes were less common. These findings support a key role for S. aureus in exacerbating CARs via antibiotic resistance, biofilm production, and the expression of virulence factor. Additionally, we emphasize the role of routine microbial screening—including nasal swabs—and therapy guided by antibiograms. Furthermore, the enzymatic score may further be validated as a predictive biomarker. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Skin Diseases (Second Edition))
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24 pages, 855 KiB  
Review
Antibody–Drug Conjugates Powered by Deruxtecan: Innovations and Challenges in Oncology
by Jung Yoon Jang, Donghwan Kim, Na Kyeong Lee, Eunok Im and Nam Deuk Kim
Int. J. Mol. Sci. 2025, 26(13), 6523; https://doi.org/10.3390/ijms26136523 - 7 Jul 2025
Viewed by 1260
Abstract
Antibody–drug conjugates (ADCs) have revolutionized precision oncology by enabling targeted drug delivery with improved therapeutic indices. Among these, deruxtecan (DXd)-based ADCs have demonstrated remarkable efficacy across a range of cancers, particularly in tumors expressing human epidermal growth factor receptor 2 (HER2), human epidermal [...] Read more.
Antibody–drug conjugates (ADCs) have revolutionized precision oncology by enabling targeted drug delivery with improved therapeutic indices. Among these, deruxtecan (DXd)-based ADCs have demonstrated remarkable efficacy across a range of cancers, particularly in tumors expressing human epidermal growth factor receptor 2 (HER2), human epidermal growth factor receptor 3 (HER3), and trophoblast cell surface antigen 2 (TROP2), including breast, lung, gastric, and other solid tumors. DXd, a potent topoisomerase I inhibitor, enhances the cytotoxic potential of ADCs through a cleavable and stable linker and a high drug-to-antibody ratio that ensures optimal drug release. The clinical success of trastuzumab DXd (Enhertu®) and datopotamab DXd (Datroway®), along with the ongoing development of patritumab DXd, has expanded the therapeutic potential of ADCs. However, challenges remain, including toxicity, resistance, and manufacturing scalability. This review discusses the mechanisms of action, clinical progress, and challenges of DXd-based ADCs, highlighting their transformative role in modern oncology and exploring future directions to optimize their efficacy and accessibility. Full article
(This article belongs to the Special Issue New Wave of Cancer Therapeutics: Challenges and Opportunities)
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22 pages, 5156 KiB  
Article
The Role of Fat Mass and Obesity-Associated (FTO) Gene in Non-Small Cell Lung Cancer Tumorigenicity and EGFR Tyrosine Kinase Inhibitor Resistance
by Aayush Rastogi, Rong Qiu, Rachel Campoli, Usama Altayeh, Sarai Arriaga, Muhammad J. Khan, Subaranjana Saravanaguru Vasanthi, Robert Hillwig and Neelu Puri
Biomedicines 2025, 13(7), 1653; https://doi.org/10.3390/biomedicines13071653 - 7 Jul 2025
Viewed by 509
Abstract
Background/Objectives: The fat mass and obesity-associated (FTO) protein demethylates nuclear N6-Methyladenosine (m6A) on mRNA, facilitates tumor growth, and contributes to therapeutic resistance in multiple cancer types. Recent evidence demonstrates several roles of FTO in tumorigenesis. In this study, we seek to explore [...] Read more.
Background/Objectives: The fat mass and obesity-associated (FTO) protein demethylates nuclear N6-Methyladenosine (m6A) on mRNA, facilitates tumor growth, and contributes to therapeutic resistance in multiple cancer types. Recent evidence demonstrates several roles of FTO in tumorigenesis. In this study, we seek to explore the role of FTO in non-small cell lung cancer (NSCLC) tumorigenicity and its relationship with epidermal growth factor receptor (EGFR) tyrosine kinase resistance. Methods: We performed qPCR, immunoblotting, viability assays, migration assays, and ATP assays to investigate the functions of FTO in EGFR tyrosine kinase inhibitor (TKI) resistance, specifically to erlotinib, in three NSCLC cell lines harboring either wild-type or mutant EGFR. We also performed immunohistochemistry on lung tumor tissues from patients diagnosed at different stages of NSCLC. Results: Our study found an upregulation of FTO in erlotinib-resistant (ER) cell lines at both the gene and protein levels. FTO inhibition and knockdown significantly reduced cell viability of erlotinib-resistant H2170 and PC9 cells by over 30% when treated with 0.8 µM of Dac51 and about 20% when treated with siFTO. FTO inhibition also slowed down the migration of ER cells, and the effect was even more pronounced when combined with erlotinib. Furthermore, FTO was found to be overexpressed in late-stage NSCLC tumor tissues compared to early-stage tumors, and it was upregulated in patients who smoked. Conclusions: These findings suggest FTO might mediate resistance and tumor growth by augmenting cell proliferation. In addition, FTO can be a potential prognostic marker in NSCLC patients. Full article
(This article belongs to the Special Issue Signaling of Protein Kinases in Development and Disease)
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15 pages, 259 KiB  
Review
Predictive Factors of Response to Neoadjuvant Chemotherapy (NACT) and Immune Checkpoint Inhibitors in Early-Stage Triple-Negative Breast Cancer Patients (TNBC)
by Khashayar Yazdanpanah Ardakani, Francesca Fulvia Pepe, Serena Capici, Thoma Dario Clementi and Marina Elena Cazzaniga
Curr. Oncol. 2025, 32(7), 387; https://doi.org/10.3390/curroncol32070387 - 4 Jul 2025
Viewed by 593
Abstract
Triple-negative breast cancer (TNBC) is a heterogenous group of breast tumors. This type of breast tumor is relatively difficult to manage, due to the lack of expression of Hormone Receptors (HR) and human epidermal growth factor receptor (HER2). Efforts have been made to [...] Read more.
Triple-negative breast cancer (TNBC) is a heterogenous group of breast tumors. This type of breast tumor is relatively difficult to manage, due to the lack of expression of Hormone Receptors (HR) and human epidermal growth factor receptor (HER2). Efforts have been made to understand the factors involved in determining how a triple-negative breast tumor responds to therapy. The standard of treatment in most cases today is a combined modality of immune checkpoint inhibitors (ICIs) and chemotherapy with agents such as anti-mitotic (taxanes) or DNA-damaging agents (alkylating agents, cyclophosphamides, platin salts). In this study, we investigated the predictive and prognostic factors for TNBC, in the neoadjuvant setting; understanding each patient’s response before treatment initiation is crucial to guiding the subsequent approach and finally improving patient outcomes. We focused on tumor-infiltrating lymphocytes at the site of the primary tumor (TILs), circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), the mutational status of protein 53 (p53), and Ki-67, investigating the potential roles of these factors in predicting responses to anti-cancer agents. Full article
(This article belongs to the Special Issue Advances in Immunotherapy for Breast Cancer)
18 pages, 1827 KiB  
Article
A Pharmacologic Approach Against Glioblastoma—A Synergistic Combination of a Quinoxaline-Based and a PI3K/mTOR Dual Inhibitor
by Vitória Santório de São José, Bruno Marques Vieira, Camila Saggioro de Figueiredo, Luis Gabriel Valdivieso Gelves, Vivaldo Moura Neto and Lídia Moreira Lima
Int. J. Mol. Sci. 2025, 26(13), 6392; https://doi.org/10.3390/ijms26136392 - 2 Jul 2025
Viewed by 421
Abstract
Glioblastoma (GB) is the most common malignant primary CNS tumor with a fast-growing and invasive profile. As a result of the poor prognosis and limited therapy available, glioblastoma shows a high mortality rate. Given the scarcity of effective chemotherapy options, multiple studies have [...] Read more.
Glioblastoma (GB) is the most common malignant primary CNS tumor with a fast-growing and invasive profile. As a result of the poor prognosis and limited therapy available, glioblastoma shows a high mortality rate. Given the scarcity of effective chemotherapy options, multiple studies have explored the potential of tyrosine kinase inhibitors. To mitigate resistance and improve potency and selectivity, we proposed the combination of a potent irreversible epidermal growth factor receptor inhibitor—LASSBio-1971—and a potent phosphatidylinositol-3-kinase/mammalian target of rapamycin dual inhibitor—Gedatolisib—through an in vitro phenotypic study using five human GB lines. Here, we aimed to establish the cytotoxic potency, selectivity, and effect on proliferation, apoptosis, migration, and the cell cycle. Our data showed the cytotoxic potency of Gedatolisib and LASSBio-1971 and improved selectivity in the GB cell lines. They highlighted the synergistic response from their combination and its impact on migration reduction, G0/G1 cell cycle arrest, GB cytotoxicity, and apoptosis-inducing effects for different GB cell lines. The drug combination studies in phenotypic in vitro models made it possible to suggest a new potential treatment for glioblastoma that justifies further safety in in vivo phases of preclinical trials with the combination. Full article
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19 pages, 4114 KiB  
Article
Proteomic Profiling Reveals TPR and FGA as Predictive Serum Biomarkers of Relapse to First- and Second-Generation EGFR-TKIs in Advanced Lung Adenocarcinoma
by Pritsana Raungrut, Wararat Chiangjong, Thipphanet Masjon, Saowanee Maungchanburi, Thidarat Ruklert and Narongwit Nakwan
Biomedicines 2025, 13(7), 1608; https://doi.org/10.3390/biomedicines13071608 - 30 Jun 2025
Viewed by 330
Abstract
Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) significantly enhance the median survival of patients with lung adenocarcinoma (ADC) that harbor EGFR-sensitive mutations. However, most patients inevitably experience tumor relapse owing to drug resistance. We aimed to identify potential serum biomarkers [...] Read more.
Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) significantly enhance the median survival of patients with lung adenocarcinoma (ADC) that harbor EGFR-sensitive mutations. However, most patients inevitably experience tumor relapse owing to drug resistance. We aimed to identify potential serum biomarkers for predicting post-EGFR-TKI treatment relapse in patients with advanced-stage lung ADC. Methods: Among 27 patients, including 6 and 21 with early and late relapse, respectively, differentially expressed proteins between patients with early and late relapses were identified using liquid chromatography and tandem mass spectrometry and subsequently validated using Western blotting. Predictive ability was assessed using the receiver operating characteristic curve and area under the curve (AUC) analysis. The association between the clinical variables and treatment response was evaluated using the chi-square test. Results: The serum expression levels of the translocated promoter region (TPR), junction plakoglobin (JUP), and fibrinogen alpha chain (FGA) were significantly higher in patients with late rather than early relapse. The findings indicated that TPR and FGA exhibited good diagnostic performance, with AUCs of 0.946 (p = 0.002; 95% confidence interval [CI], 0.84–1.05) and 0.809 (p = 0.034; 95% CI, 0.65–0.97), respectively. Conclusions: Our results suggest that the TPR and FGA levels are potential predictors of post-EGFR-TKI treatment relapse. Full article
(This article belongs to the Special Issue Advances in Lung Cancer: From Bench to Bedside)
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19 pages, 1798 KiB  
Review
Current Status of Multimodal Therapy for Oligometastatic Disease, Induced Oligometastatic Disease, and Oligo-Progressive Disease in EGFR-Mutated Non-Small-Cell Lung Cancer
by Taichi Miyawaki, Hirotsugu Kenmotsu, Ryo Ko, Masaki Oshima, Takehito Shukuya, Naoto Shikama and Kazuhisa Takahashi
Cancers 2025, 17(13), 2202; https://doi.org/10.3390/cancers17132202 - 30 Jun 2025
Viewed by 464
Abstract
Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have shown clinical activity for patients with EGFR-mutated non-small-cell lung cancer (NSCLC). However, the development of resistance to EGFR-TKIs is almost inevitable, posing a significant barrier to long-term survival. Local ablative therapy (LAT) may [...] Read more.
Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have shown clinical activity for patients with EGFR-mutated non-small-cell lung cancer (NSCLC). However, the development of resistance to EGFR-TKIs is almost inevitable, posing a significant barrier to long-term survival. Local ablative therapy (LAT) may facilitate the prolonged survival of patients with oligometastatic NSCLC. Therapeutic combinations of EGFR-TKIs and LAT for residual disease have been suggested to be potentially effective in EGFR-mutated NSCLC with induced oligometastatic disease, wherein a few lesions remain following initial EGFR-TKI treatment. Various resistance pathways for third-generation EGFR-TKIs including osimertinib, current standard of care for patients with EGFR-mutated NSCLC, have also been identified. In addition to resistance mechanisms, the disease-progression pattern may be an essential element for achieving long-term response and survival. Oligo-progressive disease is a state in which only a few lesions become resistant, whereas many lesions remain controlled with effective systemic therapy. Previous studies have shown that LAT for all oligo-progressive lesions could provide survival benefits. This review discusses the current treatment options and potential future therapeutic developments for patients with EGFR-mutated NSCLC who have synchronous oligometastatic disease, oligo-residual disease during treatment with EGFR-TKIs, and oligo-progressive disease following resistance to EGFR-TKIs. Full article
(This article belongs to the Special Issue The Current Status of Treatment for Oligometastatic Lung Cancer)
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