Search Results (7,471)

Background: Growth Differentiation Factor 15 (GDF15) has emerged as a key biomarker and therapeutic target in oncology, with roles extending beyond cancer cachexia. Elevated GDF15 levels correlate with poor prognosis across several solid tumors, including colorectal, gastric, pancreatic, breast, lung, prostate, and head and neck cancers. GDF15 modulates tumor progression through PI3K/AKT, MAPK/ERK, and SMAD2/3 signaling, thereby promoting epithelial-to-mesenchymal transition, metastasis, immune evasion, and chemoresistance via Nrf2 stabilization and oxidative stress regulation. Methods: We performed a narrative review of the literature focusing on the role of GDF15 in solid tumors, with a particular emphasis on head and neck cancers. Results: In head and neck squamous cell carcinoma (HNSCC), GDF15 overexpression is linked to aggressive phenotypes, radioresistance, poor response to induction chemotherapy, and failure of immune checkpoint inhibitors (ICIs). Similar associations are observed in colorectal, pancreatic, and prostate cancer, where GDF15 contributes to metastasis and therapy resistance. Targeting the GDF15-GFRAL axis appears therapeutically promising: the monoclonal antibody ponsegromab improved cachexia-related outcomes in the PROACC-1 trial, while visugromab combined with nivolumab enhanced immune response in ICI-refractory tumors. Conclusions: Further investigation is warranted to delineate the role of GDF15 across malignancies, refine patient selection, and evaluate combinatorial approaches with existing treatments. Full article

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

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

Female cancers such as breast and gynaecological cancers contribute to a significant global health burden and are a leading cause of fatality among women. With current treatment options often limited by resistance to cytotoxic drugs, side effects and lack of specificity to the cancer, there is a pressing need for alternative treatments. Recent research has highlighted the promising role of non-coding RNAs (ncRNA) in regulating these issues and providing more targeted approaches to suppressing key cancer pathways. This review explores the involvement of the various types of non-coding RNAs in regulating key oncogenic pathways, namely, the MAPK, PI3K/Akt/mTOR, Wnt/β-catenin and p53 pathways, in a range of female cancers such as breast, cervical, ovarian and endometrial cancers. Evidence from a multitude of studies suggests that non-coding RNAs function as double-edged swords, serving as both oncogenes and tumour suppressors, depending on their expression and cellular interactions. By mapping and investigating these regulatory interactions, this review demonstrates the complexity and dual functionality of ncRNAs in cancer. Understanding these complex mechanisms is essential for the development of new and effective ncRNA-based diagnostic methods and targeted therapies in female cancer treatment. Full article

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

Macrophage-mediated inflammation is known to be involved in the epithelial–mesenchymal transition (EMT) of various types of cancer. This makes macrophage-derived inflammatory factors prime targets for the development of new treatments. This study uncovers the therapeutic potential and action mechanism of DAB-2-28, a small-molecule derived from para-aminobenzoic acid, in the treatment of breast cancer. The luminal MCF-7 and the triple-negative MDA-MB-231 cancer cell lines used in this study represent, respectively, breast cancers in which the differentiation states are related to the epithelial phenotype of the mammary gland and breast cancers expressing a highly aggressive mesenchymal phenotype. In MCF-7 cells, soluble factors from macrophage-conditioned media (CM-MØ) induce a characteristic morphology of mesenchymal cells with an upregulated expression of Snail1, a mesenchymal marker, as opposed to a decrease in the expression of E-cadherin, an epithelial marker. DAB-2-28 does not affect the differential expression of Snail1 and E-cadherin in response to CM-MØ, but negatively impacts other hallmarks of EMT by decreasing invasion and migration capacities, in addition to MMP9 expression and gelatinase activity, in both MCF-7 and MDA-MB-231 cells. Moreover, DAB-2-28 inhibits the phosphorylation of key pro-EMT transcriptional factors, such as NFκB, STAT3, SMAD2, CREB, and/or AKT proteins, in breast cancer cells exposed to different EMT inducers. Overall, our study provides evidence suggesting that inhibition of EMT initiation or maintenance is a key mechanism by which DAB-2-28 can exert anti-tumoral effects in breast cancer cells. Full article

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

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

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

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

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

Breast cancer (BC) progression appears to be significantly influenced by the diabetic microenvironment, characterised by hyperglycaemia and hyperinsulinemia, though the exact cellular mechanisms remain partly unclear. This study investigated the effects of exposure to supra-physiological levels of glucose and insulin on two distinct BC cell models: hormone-responsive MCF-7 cells and triple-negative MDA-MB-231 cells. To evaluate the effects triggered by high insulin level in different BC cell subtypes, we analysed the activation status of PI3K/AKT and MAPK pathways, cell proliferation, cell distribution in cell cycle phases and cell migration. High insulin level significantly activates the insulin metabolic pathway via AKT phosphorylation in both cell lines while inducing pro-proliferative stimulus and modulation of cell distribution in cell cycle phases only in the hormone-responsive MCF-7 cell line. On the contrary, high-glucose containing medium alone did not modulate proliferation nor further increased it when combined with high insulin level in both the investigated cell lines. However, following insulin treatment, the MAPK pathway remained unaffected, suggesting that the proliferation effects in the MCF-7 cell line are mediated by AKT activation. This linkage was also demonstrated by AKT phosphorylation blockade, driven by the AKT inhibitor MK-2206, which negated the proliferative stimulus. Interestingly, while MDA-MB-231 cells, following chronic hyperinsulinemia exposure, did not exhibit enhanced proliferation, they displayed a marked increase in migratory behaviour. These findings suggest that chronic hyperinsulinemia, but not hyperglycaemia, exerts subtype-specific effects in BC, highlighting the potential of targeting insulin pathways for therapeutic intervention. Full article

Objectives: Surface-Guided Radiation Therapy (SGRT) has been widely adopted in breast cancer radiotherapy, particularly for improving setup accuracy and motion management. Recently, its application in lung cancer has attracted growing interest due to similar needs for precision. This study investigates the feasibility and clinical utility of SGRT in lung cancer treatment, focusing on its effectiveness in patient setup and real-time motion monitoring under frameless immobilization conditions. Materials and Methods: A total of 204 treatment records from 17 patients with primary lung cancer who underwent radiotherapy at Korea University Guro Hospital between October 2024 and April 2025 were retrospectively analyzed. Patients were initially positioned using the Identify system (Varian) in the CT suite, with surface data transferred to the treatment room system. Alignment was performed to within ±1 cm and ±2° across six degrees of freedom. Cone-beam CT (CBCT) was acquired prior to treatment for verification, and treatment commenced when the Distance to Correspondence Surface (DCS) was ≤0.90. Setup deviations from the Identify system were recorded and compared with CBCT in three translational axes to evaluate positioning accuracy and PTV displacement. Results and Conclusions: The Identify system was shown to provide high setup accuracy and reliable real-time motion monitoring in lung cancer radiotherapy. Its ability to detect patient movement and automatically interrupt beam delivery contributes to enhanced treatment safety and precision. In addition, even though the maximum longitudinal (Lng) shift reached up to −1.83 cm with surface-guided setup, and up to 1.78 cm (Lat) 5.26 cm (Lng), 9.16 cm (Vrt) with CBCT-based verification, the use of Identify’s auto-interruption mode (±1 cm in translational axes, ±2° in rotational axes) allowed treatment delivery with PTV motion constrained within ±0.02 cm. These results suggest that, due to significant motion in the longitudinal direction, appropriate PTV margins should be considered during treatment planning. The Identify system enhances setup accuracy in lung cancer patients using a surface-guided approach and enables real-time tracking of intra-fractional errors. SGRT, when implemented with systems such as Identify, shows promise as a feasible alternative or complement to conventional IGRT in selected lung cancer cases. Further studies with larger patient cohorts and diverse clinical settings are warranted to validate these findings. Full article

Nudibranchs have garnered increasing interest in biomedical research due to their complex chemical defense mechanisms, many of which are derived from their diet, including sponges, cnidarians, tunicates, and algae. Their remarkable ability to sequester dietary toxins and synthesize secondary metabolites positions them as a promising source of biologically active compounds with potential therapeutic applications, particularly in oncology. This study aimed to review and summarize the available literature on the bioactive potential of nudibranch-derived compounds, focusing mainly on their antitumor properties. Although research in this area is still limited, recent studies have identified alkaloids and terpenoids isolated from species such as Dolabella auricularia, Jorunna funebris, Dendrodoris fumata, and members of the genus Phyllidia. These compounds exhibit notable cytotoxic activity against human cancer cell lines, including those from colon (HCT-116, HT-29, SW-480), lung (A549), and breast (MCF7) cancer. These findings suggest that compounds derived from nudibranchs could serve as scaffolds for the development of more effective and selective anticancer therapies. In conclusion, nudibranchs represent a valuable yet underexplored resource for antitumor drug discovery, with significant potential to contribute to the development of novel cancer treatments. Full article

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