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19 pages, 1632 KiB  
Guidelines
Multidisciplinary Practical Guidance for Implementing Adjuvant CDK4/6 Inhibitors for Patients with HR-Positive, HER2-Negative Early Breast Cancer in Canada
by Katarzyna J. Jerzak, Sandeep Sehdev, Jean-François Boileau, Christine Brezden-Masley, Nadia Califaretti, Scott Edwards, Jenn Gordon, Jan-Willem Henning, Nathalie LeVasseur and Cindy Railton
Curr. Oncol. 2025, 32(8), 444; https://doi.org/10.3390/curroncol32080444 - 7 Aug 2025
Abstract
Cyclin-dependent kinase (CDK)4/6 inhibitors have become a key component of adjuvant treatment for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) early breast cancer who are at high risk of recurrence. The addition of abemaciclib and ribociclib to standard [...] Read more.
Cyclin-dependent kinase (CDK)4/6 inhibitors have become a key component of adjuvant treatment for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) early breast cancer who are at high risk of recurrence. The addition of abemaciclib and ribociclib to standard endocrine therapy has demonstrated clinically meaningful improvements in invasive disease-free survival, supported by the monarchE and NATALEE trials, respectively. With expansion of patient eligibility for CDK4/6 inhibitors, multidisciplinary coordination among medical oncologists, surgeons, nurses, pharmacists, and other health care providers is critical to optimizing patient identification, monitoring, and management of adverse events. This expert guidance document provides practical recommendations for implementing adjuvant CDK4/6 inhibitor therapy in routine clinical practice, incorporating insights from multiple specialties and with patient advocacy representation. Key considerations include patient selection based on clinical trial data, treatment duration, dosing schedules, adverse event profiles, monitoring requirements, drug–drug interactions, and patient-specific factors such as tolerability, cost, and quality of life. This guidance aims to support Canadian clinicians in effectively integrating CDK4/6 inhibitors into clinical practice, ensuring optimal patient outcomes through a multidisciplinary and patient-centric approach. Full article
(This article belongs to the Section Breast Cancer)
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13 pages, 1488 KiB  
Article
Validation of a Quantitative Ultrasound Texture Analysis Model for Early Prediction of Neoadjuvant Chemotherapy Response in Breast Cancer: A Prospective Serial Imaging Study
by Daniel Moore-Palhares, Lakshmanan Sannachi, Adrian Wai Chan, Archya Dasgupta, Daniel DiCenzo, Sonal Gandhi, Rossanna Pezo, Andrea Eisen, Ellen Warner, Frances Wright, Nicole Look Hong, Ali Sadeghi-Naini, Mia Skarpathiotakis, Belinda Curpen, Carrie Betel, Michael C. Kolios, Maureen Trudeau and Gregory J. Czarnota
Cancers 2025, 17(15), 2594; https://doi.org/10.3390/cancers17152594 - 7 Aug 2025
Abstract
Background/Objectives: Patients with breast cancer who do not achieve a complete response to neoadjuvant chemotherapy (NAC) may benefit from intensified adjuvant systemic therapy. However, such treatment escalation is typically delayed until after tumour resection, which occurs several months into the treatment course. Quantitative [...] Read more.
Background/Objectives: Patients with breast cancer who do not achieve a complete response to neoadjuvant chemotherapy (NAC) may benefit from intensified adjuvant systemic therapy. However, such treatment escalation is typically delayed until after tumour resection, which occurs several months into the treatment course. Quantitative ultrasound (QUS) can detect early microstructural changes in tumours and may enable timely identification of non-responders during NAC, allowing for earlier treatment intensification. In our previous prospective observational study, 100 breast cancer patients underwent QUS imaging before and four times during NAC. Machine learning algorithms based on QUS texture features acquired in the first week of treatment were developed and achieved 78% accuracy in predicting treatment response. In the current study, we aimed to validate these algorithms in an independent prospective cohort to assess reproducibility and confirm their clinical utility. Methods: We included breast cancer patients eligible for NAC per standard of care, with tumours larger than 1.5 cm. QUS imaging was acquired at baseline and during the first week of treatment. Tumour response was defined as a ≥30% reduction in target lesion size on the resection specimen compared to baseline imaging. Results: A total of 51 patients treated between 2018 and 2021 were included (median age 49 years; median tumour size 3.6 cm). Most were estrogen receptor–positive (65%) or HER2-positive (33%), and the majority received dose-dense AC-T (n = 34, 67%) or FEC-D (n = 15, 29%) chemotherapy, with or without trastuzumab. The support vector machine algorithm achieved an area under the curve of 0.71, with 86% accuracy, 91% specificity, 50% sensitivity, 93% negative predictive value, and 43% positive predictive value for predicting treatment response. Misclassifications were primarily associated with poorly defined tumours and difficulties in accurately identifying the region of interest. Conclusions: Our findings validate QUS-based machine learning models for early prediction of chemotherapy response and support their potential as non-invasive tools for treatment personalization and clinical trial development focused on early treatment intensification. Full article
(This article belongs to the Special Issue Clinical Applications of Ultrasound in Cancer Imaging and Treatment)
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12 pages, 486 KiB  
Article
Efficacy and Safety of Dose-Dense Chemotherapy in Breast Cancer: Real Clinical Data and Literature Review
by Keiko Yanagihara, Masato Yoshida, Tamami Yamakawa, Sena Kato, Miki Tamura and Koji Nagata
Curr. Oncol. 2025, 32(8), 441; https://doi.org/10.3390/curroncol32080441 - 6 Aug 2025
Abstract
Dose-dense chemotherapy shortens the interval between chemotherapy cycles and has shown improved outcomes in high-risk breast cancer patients. We retrospectively evaluated the efficacy and safety of dose-dense chemotherapy in 80 breast cancer patients treated at our hospital from 2020 to 2024. The regimen [...] Read more.
Dose-dense chemotherapy shortens the interval between chemotherapy cycles and has shown improved outcomes in high-risk breast cancer patients. We retrospectively evaluated the efficacy and safety of dose-dense chemotherapy in 80 breast cancer patients treated at our hospital from 2020 to 2024. The regimen included epirubicin and cyclophosphamide followed by paclitaxel or docetaxel, with pegfilgrastim support. The overall treatment completion rate was 82.5%. Of the 80 patients, 55 underwent neoadjuvant chemotherapy, and the pathological complete response rate was significantly higher in triple-negative breast cancer (59.1%) compared to that in luminal-type cancer (9.1%). Common adverse events included anemia, liver dysfunction, myalgia, and peripheral neuropathy. Febrile neutropenia occurred in 8.8% of patients, with some cases linked to pegfilgrastim body pod use, particularly in individuals with low subcutaneous fat. Notably, two patients developed pneumocystis pneumonia, potentially associated with steroid administration. Despite these toxicities, most were manageable and resolved after treatment. Our findings support the efficacy of dose-dense chemotherapy, particularly in triple-negative breast cancer, while highlighting the importance of individualized supportive care and vigilance regarding hematologic and infectious complications. Full article
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16 pages, 1701 KiB  
Article
Aromatase Inhibitor-Induced Carpal Tunnel Syndrome Immunohistochemical Analysis and Clinical Evaluation: An Observational, Cross-Sectional, Case–Control Study
by Iakov Molayem, Lucian Lior Marcovici, Roberto Gradini, Massimiliano Mancini, Silvia Taccogna and Alessia Pagnotta
J. Clin. Med. 2025, 14(15), 5513; https://doi.org/10.3390/jcm14155513 - 5 Aug 2025
Abstract
Background/Objectives: Breast cancer was the leading cause of malignant tumors among women in 2022. About two-thirds of breast cancer cases are hormone-receptor-positive. In these patients, aromatase inhibitors are a mainstay of treatment, but associated musculoskeletal symptoms can negatively affect patient compliance. Aromatase-inhibitor-induced [...] Read more.
Background/Objectives: Breast cancer was the leading cause of malignant tumors among women in 2022. About two-thirds of breast cancer cases are hormone-receptor-positive. In these patients, aromatase inhibitors are a mainstay of treatment, but associated musculoskeletal symptoms can negatively affect patient compliance. Aromatase-inhibitor-induced carpal tunnel syndrome represents one of the main causes of aromatase inhibitor discontinuation, with a non-compliance rate of up to 67%, potentially leading to increased cancer mortality. This study investigates estrogen receptor expression in aromatase-inhibitor-induced carpal tunnel syndrome tissues, in order to better define its etiopathogenesis and derive preventive or therapeutic measures that can improve aromatase inhibitor patient compliance. To our knowledge, there is no study on this subject in the literature. Methods: Between 2023 and 2024, we recruited 14 patients at the Jewish Hospital of Rome, including seven patients with aromatase-inhibitor-induced carpal tunnel syndrome (study group) and seven with postmenopausal idiopathic carpal tunnel syndrome (control group). Each patient was evaluated based on a clinical visit, a questionnaire, instrumental exams, and serum hormone dosages and were treated with open carpal tunnel release surgery, during which transverse carpal ligament and flexor tenosynovium samples were collected. For immunohistochemical experiments, sections were treated with anti-estrogen receptor α and anti-estrogen receptor β antibodies. Results: The immunohistochemical features in the study and control groups were similar, demonstrating that tissues affected by aromatase-inhibitor-induced carpal tunnel syndrome are targets of direct estrogen action and that estrogen deprivation is correlated with disease etiogenesis. Surgery was effective in patient treatment. Conclusions: Aromatase-inhibitor-induced carpal tunnel syndrome represents a newly defined form of the disease. This syndrome represents one of the main causes of aromatase inhibitor discontinuation, due to its negative impact on the patient’s quality of life. The identification by clinicians of aromatase inhibitor use as a possible risk factor for carpal tunnel syndrome development is of essential importance, as early diagnosis and prompt management can improve patient compliance and overall breast cancer treatment outcomes. Full article
(This article belongs to the Section General Surgery)
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14 pages, 2501 KiB  
Article
Therapeutic Patterns and Surgical Decision-Making in Breast Cancer: A Retrospective Regional Cohort Study in Romania
by Ramona Andreea Cioroianu, Michael Schenker, Virginia-Maria Rădulescu, Tradian Ciprian Berisha, George Ovidiu Cioroianu, Mihaela Popescu, Cristina Mihaela Ciofiac, Ana Maria Petrescu and Stelian Ștefăniță Mogoantă
Clin. Pract. 2025, 15(8), 145; https://doi.org/10.3390/clinpract15080145 - 5 Aug 2025
Abstract
Background: Breast cancer is the most prevalent malignancy among women globally. In Romania, it is the most frequent form of cancer affecting women, with approximately 12,000 new cases diagnosed annually, and the second most common cause of cancer-related mortality, second only to [...] Read more.
Background: Breast cancer is the most prevalent malignancy among women globally. In Romania, it is the most frequent form of cancer affecting women, with approximately 12,000 new cases diagnosed annually, and the second most common cause of cancer-related mortality, second only to lung cancer. Methods: This study looked at 79 breast cancer patients from Oltenia, concentrating on epidemiology, histology, diagnostic features, and treatments. Patients were chosen based on inclusion criteria such as histopathologically verified diagnosis, availability of clinical and treatment data, and follow-up information. The analyzed biological material consisted of tissue samples taken from the breast parenchyma and axillary lymph nodes. Even though not the primary subject of this paper, all patients underwent immunohistochemical (IHC) evaluation both preoperatively and postoperatively. Results: We found invasive ductal carcinoma to be the predominant type, while ductal carcinoma in situ (DCIS) and mixed types were rare. We performed cross-tabulations of metastasis versus nodal status and age versus therapy type; none reached significance (all p > 0.05), suggesting observed differences were likely due to chance. A chi-square test comparing surgical interventions (breast-conserving vs. mastectomy) in patients who did or did not receive chemotherapy showed, χ2 = 3.17, p = 0.367, indicating that chemotherapy did not significantly influence surgical choice. Importantly, adjuvant chemotherapy and radiotherapy were used at similar rates across age groups, whereas neoadjuvant hormonal (endocrine) therapy was more common in older patients (but without statistical significance). Conclusions: Finally, we discussed the consequences of individualized care and early detection. Romania’s shockingly low screening rate, which contributes to delayed diagnosis, emphasizes the importance of improved population medical examination and tailored treatment options. Also, the country has one of the lowest rates of mammography uptake in Europe and no systematic population screening program. Full article
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24 pages, 3788 KiB  
Review
Advances in Photoacoustic Imaging of Breast Cancer
by Yang Wu, Keer Huang, Guoxiong Chen and Li Lin
Sensors 2025, 25(15), 4812; https://doi.org/10.3390/s25154812 - 5 Aug 2025
Abstract
Breast cancer is the leading cause of cancer-related mortality among women world-wide, and early screening is critical for improving patient survival. Medical imaging plays a central role in breast cancer screening, diagnosis, and treatment monitoring. However, conventional imaging modalities—including mammography, ultrasound, and magnetic [...] Read more.
Breast cancer is the leading cause of cancer-related mortality among women world-wide, and early screening is critical for improving patient survival. Medical imaging plays a central role in breast cancer screening, diagnosis, and treatment monitoring. However, conventional imaging modalities—including mammography, ultrasound, and magnetic resonance imaging—face limitations such as low diagnostic specificity, relatively slow imaging speed, ionizing radiation exposure, and dependence on exogenous contrast agents. Photoacoustic imaging (PAI), a novel hybrid imaging technique that combines optical contrast with ultrasonic spatial resolution, has shown great promise in addressing these challenges. By revealing anatomical, functional, and molecular features of the breast tumor microenvironment, PAI offers high spatial resolution, rapid imaging, and minimal operator dependence. This review outlines the fundamental principles of PAI and systematically examines recent advances in its application to breast cancer screening, diagnosis, and therapeutic evaluation. Furthermore, we discuss the translational potential of PAI as an emerging breast imaging modality, complementing existing clinical techniques. Full article
(This article belongs to the Special Issue Optical Imaging for Medical Applications)
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34 pages, 1543 KiB  
Review
Treatment Strategies for Cutaneous and Oral Mucosal Side Effects of Oncological Treatment in Breast Cancer: A Comprehensive Review
by Sanja Brnić, Bruno Špiljak, Lucija Zanze, Ema Barac, Robert Likić and Liborija Lugović-Mihić
Biomedicines 2025, 13(8), 1901; https://doi.org/10.3390/biomedicines13081901 - 4 Aug 2025
Viewed by 240
Abstract
Cutaneous and oral mucosal adverse events (AEs) are among the most common non-hematologic toxicities observed during breast cancer treatment. These complications arise across various therapeutic modalities including chemotherapy, targeted therapy, hormonal therapy, radiotherapy, and immunotherapy. Although often underrecognized compared with systemic side effects, [...] Read more.
Cutaneous and oral mucosal adverse events (AEs) are among the most common non-hematologic toxicities observed during breast cancer treatment. These complications arise across various therapeutic modalities including chemotherapy, targeted therapy, hormonal therapy, radiotherapy, and immunotherapy. Although often underrecognized compared with systemic side effects, dermatologic and mucosal toxicities can severely impact the patients’ quality of life, leading to psychosocial distress, pain, and reduced treatment adherence. In severe cases, these toxicities may necessitate dose reductions, treatment delays, or discontinuation, thereby compromising oncologic outcomes. The growing use of precision medicine and novel targeted agents has broadened the spectrum of AEs, with some therapies linked to distinct dermatologic syndromes and mucosal complications such as mucositis, xerostomia, and lichenoid reactions. Early detection, accurate classification, and timely multidisciplinary management are essential for mitigating these effects. This review provides a comprehensive synthesis of current knowledge on cutaneous and oral mucosal toxicities associated with modern breast cancer therapies. Particular attention is given to clinical presentation, underlying pathophysiology, incidence, and evidence-based prevention and management strategies. We also explore emerging approaches, including nanoparticle-based delivery systems and personalized interventions, which may reduce toxicity without compromising therapeutic efficacy. By emphasizing the integration of dermatologic and mucosal care, this review aims to support clinicians in preserving treatment adherence and enhancing the overall therapeutic experience in breast cancer patients. The novelty of this review lies in its dual focus on cutaneous and oral complications across all major therapeutic classes, including recent biologic and immunotherapeutic agents, and its emphasis on multidisciplinary, patient-centered strategies. Full article
(This article belongs to the Section Cancer Biology and Oncology)
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26 pages, 1978 KiB  
Article
Fluorescent Peptides Internalize HeLa Cells and Kill Multidrug-Resistant Clinical Bacterial Isolates
by Daniel Castellar-Almonacid, Kelin Johana Cuero-Amu, Jose David Mendoza-Mendoza, Natalia Ardila-Chantré, Fernando José Chavez-Salazar, Andrea Carolina Barragán-Cárdenas, Jhon Erick Rivera-Monroy, Claudia Parra-Giraldo, Zuly Jenny Rivera-Monroy, Javier García-Castañeda and Ricardo Fierro-Medina
Antibiotics 2025, 14(8), 793; https://doi.org/10.3390/antibiotics14080793 - 4 Aug 2025
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Abstract
Palindromic antimicrobial peptides (PAMs) constitute versatile scaffolds for the design and optimization of anticancer agents with applications in therapy, diagnosis, and/or monitoring. In the present study, fluorolabeled peptides derived from the palindromic sequence RWQWRWQWR containing fluorescent probes, such as 2-Aminobenzoyl, 5(6)-Carboxyfluorescein, and Rhodamine [...] Read more.
Palindromic antimicrobial peptides (PAMs) constitute versatile scaffolds for the design and optimization of anticancer agents with applications in therapy, diagnosis, and/or monitoring. In the present study, fluorolabeled peptides derived from the palindromic sequence RWQWRWQWR containing fluorescent probes, such as 2-Aminobenzoyl, 5(6)-Carboxyfluorescein, and Rhodamine B, were obtained. RP-HPLC analysis revealed that the palindromic peptide conjugated to Rhodamine B (RhB-RWQWRWQWR) exhibited the presence of isomers, likely corresponding to the open-ring and spiro-lactam forms of the fluorescent probe. This equilibrium is dependent on the peptide sequence, as the RP-HPLC analysis of dimeric peptide (RhB-RRWQWR-hF-KKLG)2K-Ahx did not reveal the presence of isomers. The antibacterial activity of the fluorescent peptides depends on the probe attached to the sequence and the bacterial strain tested. Notably, some fluorescent peptides showed activity against reference strains as well as sensitive, resistant, and multidrug-resistant clinical isolates of E. coli, S. aureus, and E. faecalis. Fluorolabeled peptides 1-Abz (MIC = 62 µM), RhB-1 (MIC = 62 µM), and Abz-1 (MIC = 31 µM) exhibited significant activity against clinical isolates of E. coli, S. aureus, and E. faecalis, respectively. The RhB-1 (IC50 = 61 µM), Abz-1 (IC50 = 87 µM), and RhB-2 (IC50 = 35 µM) peptides exhibited a rapid, significant, and concentration-dependent cytotoxic effect on HeLa cells, accompanied by morphological changes characteristic of apoptosis. RhB-1 (IC50 = 18 µM) peptide also exhibited significant cytotoxic activity against breast cancer cells MCF-7. These conjugates remain valuable for elucidating the possible mechanisms of action of these novel anticancer peptides. Rhodamine-labeled peptides displayed cytotoxicity comparable to that of their unlabeled analogues, suggesting that cellular internalization constitutes a critical early step in their mechanism of action. These findings suggest that cell death induced by both unlabeled and fluorolabeled peptides proceeds predominantly via apoptosis and is likely contingent upon peptide internalization. Functionalization at the N-terminal end of the palindromic sequence can be evaluated to develop systems for transporting non-protein molecules into cancer cells. Full article
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16 pages, 2030 KiB  
Article
Myocardial Strain Measurements Obtained with Fast-Strain-Encoded Cardiac Magnetic Resonance for the Risk Prediction and Early Detection of Chemotherapy-Related Cardiotoxicity Compared to Left Ventricular Ejection Fraction
by Daniel Lenihan, James Whayne, Farouk Osman, Rafael Rivero, Moritz Montenbruck, Arne Kristian Schwarz, Sebastian Kelle, Pia Wülfing, Susan Dent, Florian Andre, Norbert Frey, Grigorios Korosoglou and Henning Steen
Diagnostics 2025, 15(15), 1948; https://doi.org/10.3390/diagnostics15151948 - 3 Aug 2025
Viewed by 267
Abstract
Background: Breast and hematological cancer treatments, especially with anthracyclines, have been shown to be associated with an increased risk of cardiotoxicity (CTX). An accurate prediction of cardiotoxicity risk and early detection of myocardial injury may allow for effective cardioprotection to be instituted and [...] Read more.
Background: Breast and hematological cancer treatments, especially with anthracyclines, have been shown to be associated with an increased risk of cardiotoxicity (CTX). An accurate prediction of cardiotoxicity risk and early detection of myocardial injury may allow for effective cardioprotection to be instituted and tailored to reverse cardiac dysfunction and prevent the discontinuation of essential cancer treatments. Objectives: The PRoactive Evaluation of Function to Evade Cardio Toxicity (PREFECT) study sought to evaluate the ability of fast-strain-encoded (F-SENC) cardiac magnetic resonance imaging (CMR) and 2D echocardiography (2D Echo) to stratify patients at risk of CTX prior to initiating cancer treatment, detect early signs of cardiac dysfunction, including subclinical CTX (sub-CTX) and CTX, and monitor for recovery (REC) during cardioprotective therapy. Methods: Fifty-nine patients with breast cancer or lymphoma were prospectively monitored for CTX with F-SENC CMR and 2D Echo over at least 1 year for evidence of cardiac dysfunction during anthracycline based chemotherapy. F-SENC CMR also monitored myocardial deformation in 37 left ventricular (LV) segments to obtain a MyoHealth risk score based on both longitudinal and circumferential strain. Sub-CTX and CTX were classified based on pre-specified cardiotoxicity definitions. Results: CTX was observed in 9/59 (15%) and sub-CTX in 24/59 (41%) patients undergoing chemotherapy. F-SENC CMR parameters at baseline predicted CTX with a lower LVEF (57 ± 5% vs. 61 ± 5% for all, p = 0.05), as well as a lower MyoHealth (70 ± 9 vs. 79 ± 11 for all, p = 0.004) and a worse global circumferential strain (GCS) (−18 ± 1 vs. −20 ± 1 for all, p < 0.001). Pre-chemotherapy MyoHealth had a higher accuracy in predicting the development of CTX compared to CMR LVEF and 2D Echo LVEF (AUC = 0.85, 0.69, and 0.57, respectively). The 2D Echo parameters on baseline imaging did not stratify CTX risk. F-SENC CMR obtained good or excellent images in 320/322 (99.4%) scans. During cancer treatment, MyoHealth had a high accuracy of detecting sub-CTX or CTX (AUC = 0.950), and the highest log likelihood ratio (indicating a higher probability of detecting CTX) followed by F-SENC GLS and F-SENC GCS. CMR LVEF and CMR LV stroke volume index (LVSVI) also significantly worsened in patients developing CTX during cancer treatment. Conclusions: F-SENC CMR provided a reliable and accurate assessment of myocardial function during anthracycline-based chemotherapy, and demonstrated accurate early detection of CTX. In addition, MyoHealth allows for the robust identification of patients at risk for CTX prior to treatment with higher accuracy than LVEF. Full article
(This article belongs to the Special Issue New Perspectives in Cardiac Imaging)
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34 pages, 10887 KiB  
Article
Heteroaryl-Capped Hydroxamic Acid Derivatives with Varied Linkers: Synthesis and Anticancer Evaluation with Various Apoptosis Analyses in Breast Cancer Cells, Including Docking, Simulation, DFT, and ADMET Studies
by Ekta Shirbhate, Biplob Koch, Vaibhav Singh, Akanksha Dubey, Haya Khader Ahmad Yasin and Harish Rajak
Pharmaceuticals 2025, 18(8), 1148; https://doi.org/10.3390/ph18081148 - 1 Aug 2025
Viewed by 170
Abstract
Background/Objectives: Cancer suffers from unresolved therapeutic challenges owing to the lack of targeted therapies and heightened recurrence risk. This study aimed to investigate the new series of hydroxamate by structurally modifying the pharmacophore of vorinostat. Methods: The present work involves the synthesis of [...] Read more.
Background/Objectives: Cancer suffers from unresolved therapeutic challenges owing to the lack of targeted therapies and heightened recurrence risk. This study aimed to investigate the new series of hydroxamate by structurally modifying the pharmacophore of vorinostat. Methods: The present work involves the synthesis of 15 differently substituted 2H-1,2,3-triazole-based hydroxamide analogs by employing triazole ring as a cap with varied linker fragments. The compounds were evaluated for their anticancer effect, especially their anti-breast cancer response. Molecular docking and molecular dynamics simulations were conducted to examine binding interactions. Results: Results indicated that among all synthesized hybrids, the molecule VI(i) inhibits the growth of MCF-7 and A-549 cells (GI50 < 10 μg/mL) in an antiproliferative assay. Compound VI(i) was also tested for cytotoxic activity by employing an MTT assay against A549, MCF-7, and MDA-MB-231 cell lines, and the findings indicate its potent anticancer response, especially against MCF-7 cells with IC50 of 60 µg/mL. However, it experiences minimal toxicity towards the normal cell line (HEK-293). Mechanistic studies revealed a dual-pathway activation: first, apoptosis (17.18% of early and 10.22% of late apoptotic cells by annexin V/PI analysis); second, cell cycle arrest at the S and G2/M phases. It also promotes ROS generation in a concentration-dependent manner. The HDAC–inhibitory assay, extended in silico molecular docking, and MD simulation experiments further validated its significant binding affinity towards HDAC 1 and 6 isoforms. DFT and ADMET screening further support the biological proclivity of the title compounds. The notable biological contribution of VI(i) highlights it as a potential candidate, especially against breast cancer cells. Full article
(This article belongs to the Section Medicinal Chemistry)
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17 pages, 14783 KiB  
Article
Behavior of Osteoblastic Lineage Cells When in the Presence of Tamoxifen: In Vitro and In Vivo Studies on Osseointegration
by Luiz Guilherme Fiorin, Emanuela Galliera, Henrique R. Matheus, Dolaji Henin, Edilson Ervolino, Gabriela Carrara Simionato, Juliano Milanezi de Almeida and Claudia Dellavia
Dent. J. 2025, 13(8), 351; https://doi.org/10.3390/dj13080351 - 1 Aug 2025
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Abstract
Background/Objectives: Tamoxifen, a selective estrogen receptor modulator widely used as an adjunct in the treatment of breast cancer, has known effects on bone metabolism, although its impact on osseointegration and cellular responses during early bone healing remains unclear. Understanding these effects is essential [...] Read more.
Background/Objectives: Tamoxifen, a selective estrogen receptor modulator widely used as an adjunct in the treatment of breast cancer, has known effects on bone metabolism, although its impact on osseointegration and cellular responses during early bone healing remains unclear. Understanding these effects is essential given the increasing use of dental implants in cancer survivors. The study aimed to observe the influence of tamoxifen on human osteosarcoma (SAOS-2) cells lines, as well on the osseointegration of titanium implants in ovariectomized female rats. Methods: SAOS-2 cells were incubated with Dulbecco’s modified growth medium. Six titanium (Ti) disks were used at each time point. The samples were divided into groups with the presence (TAM, n = 36) or not (CTR, n = 36) of tamoxifen in a concentration of 2 μM. In vivo, 72 animals were divided in groups with bilateral ovariectomy or SHAM and tamoxifen administration or not (15 mg/kg). Cell viability, mineralization rate, and collagen synthesis were assessed, as well as bone/implant contact (BIC) and bone ingrowth (BIN). Results: Tamoxifen caused a decrease in SAOS-2 viability, although an increase in the mineralization rate was observed. In vivo, the TAM groups presented higher BIC and BIN when compared to their control, but a lower percentage of mature collagen cells. Conclusions: Based on our findings, in vitro, the therapy with TAM slightly reduced the viability of SAOS-2 cells while significantly increasing the mineralization rate. In vivo, the therapy positively influenced BIC and BIN during the osseointegration phase. Full article
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14 pages, 1279 KiB  
Article
Real-World Toxicity and Effectiveness Study of Abemaciclib in Greek Patients with Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer: A Multi-Institutional Study
by Elena Fountzilas, Eleni Aravantinou-Fatorou, Katerina Dadouli, Panagiota Economopoulou, Dimitrios Tryfonopoulos, Anastasia Vernadou, Eleftherios Vorrias, Anastasios Vagionas, Adamantia Nikolaidi, Sofia Karageorgopoulou, Anna Koumarianou, Ioannis Boukovinas, Davide Mauri, Stefania Kokkali, Athina Christopoulou, Nikolaos Tsoukalas, Avraam Assi, Nikolaos Spathas, Paris Kosmidis, Angelos Koutras, George Fountzilas and Amanda Psyrriadd Show full author list remove Hide full author list
Cancers 2025, 17(15), 2543; https://doi.org/10.3390/cancers17152543 - 31 Jul 2025
Viewed by 157
Abstract
Background/Objectives: This study aimed to assess real-world toxicity and efficacy data of patients with early and advanced breast cancer (BC) who received treatment with abemaciclib. Methods: This was a prospective/retrospective multi-institutional collection of clinicopathological, toxicity, and outcome data from patients with early or [...] Read more.
Background/Objectives: This study aimed to assess real-world toxicity and efficacy data of patients with early and advanced breast cancer (BC) who received treatment with abemaciclib. Methods: This was a prospective/retrospective multi-institutional collection of clinicopathological, toxicity, and outcome data from patients with early or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative BC who received treatment with abemaciclib in combination with endocrine therapy in departments of oncology in Greece. Treatment combinations of abemaciclib with any endocrine therapy were accepted. The primary end point was toxicity rate in all patients of the study. Results: From June/2021 to May/2024, 245 women received abemaciclib/endocrine combination therapy; the median age was 57 years. Of these, 169 (69%) received abemaciclib as adjuvant therapy for early-stage disease, while 76 (31%) were treated for advanced BC. At the time of the data cutoff, 133 (84.7%) patients remained in the 2-year treatment period. The most common adverse event (AE) was diarrhea (51%), primarily Grade ≤ 2. Dose modifications due to AEs were required in 19.2% of cases, while treatment discontinuation occurred in 5.1%. There was no difference in dose modification/discontinuation rates between older patients (>65 years) and the remaining patients. For early-stage BC patients, the 2-year DFS and OS rates were 90.8% and 100%, respectively. In patients with advanced cancer (70, 30.8%), 1-year PFS and OS rates were 78% and 96.3%, respectively. Conclusions: This study confirms the safety and effectiveness of abemaciclib in alignment with registrational trials offering valuable insights into toxicity management and clinical outcomes in routine practice without identifying new safety concerns. Clinical Trial Registration: ClinicalTrials.gov NCT04985058. Full article
(This article belongs to the Section Cancer Survivorship and Quality of Life)
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18 pages, 432 KiB  
Article
Anthropometry and the Risk of Breast Cancer in Moroccan Women: A Large Multicentric Case-Control Study
by Najia Mane, Najoua Lamchabbek, Siham Mrah, Mohammed Saidi, Chaimaa Elattabi, Elodie Faure, Fatima Zahra El M’rabet, Adil Najdi, Nawfel Mellas, Karima Bendahou, Lahcen Belyamani, Boutayeb Saber, Karima El Rhazi, Chakib Nejjari, Inge Huybrechts and Mohamed Khalis
Curr. Oncol. 2025, 32(8), 434; https://doi.org/10.3390/curroncol32080434 - 31 Jul 2025
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Abstract
Although evidence suggests adiposity as a modifiable risk factor for postmenopausal breast cancer (BC), its association with premenopausal BC remains uncertain. This potential differential relationship for menopausal status has been insufficiently investigated in the Moroccan population due to limited data. This study aims [...] Read more.
Although evidence suggests adiposity as a modifiable risk factor for postmenopausal breast cancer (BC), its association with premenopausal BC remains uncertain. This potential differential relationship for menopausal status has been insufficiently investigated in the Moroccan population due to limited data. This study aims to assess the relationship between various indicators of adiposity and the risk of BC among Moroccan women by menopausal status. A multicenter case-control study was conducted in Morocco between December 2019 and August 2023, including 1400 incident BC cases and 1400 matched controls. Detailed measures of adiposity and self-reported measures from different life stages were collected. Unconditional logistic regression analyses were conducted to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association between body size indicators and the risk of BC, adjusting for a range of known risk factors for BC. Higher waist circumference (WC) and hip circumference (HC) were associated with an increased risk of BC in both pre- (p-trend < 0.001 for both WC and HC) and post-menopausal women (p-trend < 0.001 for WC, 0.002 for HC). Current body mass index (BMI) ≥30 kg/m2 increased the risk of postmenopausal BC (p-trend = 0.012). Among postmenopausal women, higher weight at age 20 was positively associated with BC risk (p-trend < 0.001), while, weight at age 30 was significantly associated with increased BC risk in both pre- (p-trend = 0.008) and post-menopausal women (p-trend = 0.028). Interestingly, weight gain since age 20 was inversely associated with BC risk in postmenopausal women in the adjusted model (p-trend = 0.006). Young-adult BMI observed a significant increased trend with BC risk in both pre- (p-trend = 0.008) and post-menopausal women (p-trend < 0.001). In premenopausal women, larger body shape during childhood and early adulthood was positively associated with BC risk (p-trend = 0.01 and = 0.011, respectively). In postmenopausal women, larger childhood and adolescent body silhouettes were also associated with increased BC risk (p-trend = 0.045 and 0.047, respectively). These results suggest that anthropometric factors may have different associations with pre- and post-menopausal BC among Moroccan women. This underscores the importance of conducting large prospective studies to better understand these findings and explore their links to different molecular subtypes of BC. Full article
(This article belongs to the Section Breast Cancer)
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38 pages, 2158 KiB  
Review
Epigenetic Modulation and Bone Metastasis: Evolving Therapeutic Strategies
by Mahmoud Zhra, Jasmine Hanafy Holail and Khalid S. Mohammad
Pharmaceuticals 2025, 18(8), 1140; https://doi.org/10.3390/ph18081140 - 31 Jul 2025
Viewed by 496
Abstract
Bone metastasis remains a significant cause of morbidity and diminished quality of life in patients with advanced breast, prostate, and lung cancers. Emerging research highlights the pivotal role of reversible epigenetic alterations, including DNA methylation, histone modifications, chromatin remodeling complex dysregulation, and non-coding [...] Read more.
Bone metastasis remains a significant cause of morbidity and diminished quality of life in patients with advanced breast, prostate, and lung cancers. Emerging research highlights the pivotal role of reversible epigenetic alterations, including DNA methylation, histone modifications, chromatin remodeling complex dysregulation, and non-coding RNA networks, in orchestrating each phase of skeletal colonization. Site-specific promoter hypermethylation of tumor suppressor genes such as HIN-1 and RASSF1A, alongside global DNA hypomethylation that activates metastasis-associated genes, contributes to cancer cell plasticity and facilitates epithelial-to-mesenchymal transition (EMT). Key histone modifiers, including KLF5, EZH2, and the demethylases KDM4/6, regulate osteoclastogenic signaling pathways and the transition between metastatic dormancy and reactivation. Simultaneously, SWI/SNF chromatin remodelers such as BRG1 and BRM reconfigure enhancer–promoter interactions that promote bone tropism. Non-coding RNAs, including miRNAs, lncRNAs, and circRNAs (e.g., miR-34a, NORAD, circIKBKB), circulate via exosomes to modulate the RANKL/OPG axis, thereby conditioning the bone microenvironment and fostering the formation of a pre-metastatic niche. These mechanistic insights have accelerated the development of epigenetic therapies. DNA methyltransferase inhibitors (e.g., decitabine, guadecitabine) have shown promise in attenuating osteoclast differentiation, while histone deacetylase inhibitors display context-dependent effects on tumor progression and bone remodeling. Inhibitors targeting EZH2, BET proteins, and KDM1A are now advancing through early-phase clinical trials, often in combination with bisphosphonates or immune checkpoint inhibitors. Moreover, novel approaches such as CRISPR/dCas9-based epigenome editing and RNA-targeted therapies offer locus-specific reprogramming potential. Together, these advances position epigenetic modulation as a promising axis in precision oncology aimed at interrupting the pathological crosstalk between tumor cells and the bone microenvironment. This review synthesizes current mechanistic understanding, evaluates the therapeutic landscape, and outlines the translational challenges ahead in leveraging epigenetic science to prevent and treat bone metastases. Full article
(This article belongs to the Section Biopharmaceuticals)
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25 pages, 7320 KiB  
Article
A Comprehensive Evaluation of a Chalcone Derivative: Structural, Spectroscopic, Computational, Electrochemical, and Pharmacological Perspectives
by Rekha K. Hebasur, Varsha V. Koppal, Deepak A. Yaraguppi, Neelamma B. Gummagol, Raviraj Kusanur and Ninganagouda R. Patil
Photochem 2025, 5(3), 20; https://doi.org/10.3390/photochem5030020 - 30 Jul 2025
Viewed by 210
Abstract
This study details how 3-(naphthalen-2-yl)-1-phenylprop-2-en-1-one (3NPEO) behaves in terms of photophysics when exposed to different solvents. The solvatochromic effect study reveals significant polarity shifts in the excited states of the 3NPEO compound, likely due to an intramolecular proton transfer mechanism. Measurements of dipole [...] Read more.
This study details how 3-(naphthalen-2-yl)-1-phenylprop-2-en-1-one (3NPEO) behaves in terms of photophysics when exposed to different solvents. The solvatochromic effect study reveals significant polarity shifts in the excited states of the 3NPEO compound, likely due to an intramolecular proton transfer mechanism. Measurements of dipole moments provide insight into their resonance structures in both ground and excited states. Electrochemical analysis revealed a reversible redox process, indicating a favorable charge transport potential. HOMO and LUMO energies of the compound were computed via oxidation and reduction potential standards. 3NPEO exhibits optimal one-photon and two-photon absorption characteristics, validating its suitability for visible wavelength laser applications in photonic devices. Furthermore, molecular docking and dynamics simulations demonstrated strong interactions between 3NPEO and the progesterone receptor enzyme, supported by structure–activity relationship (SAR) analyses. In vitro cytotoxicity assays on the MDAMB-231 breast cancer cell line showed moderate tumor cell inhibitory activity. Apoptosis studies confirmed the induction of both early and late apoptosis. These findings suggest that 3NPEO holds promise as a potential anticancer agent targeting the progesterone receptor in breast cancer cells. Overall, the findings highlight the substantial influence of solvent polarity on the photophysical properties and the design of more effective and stable therapeutic agents. Full article
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