INTRODUCTION: Neoadjuvant therapy has been proposed as a safe and effective treatment option for resectable colon cancer, providing several advantages over the current standard adjuvant protocol. AREAS COVERED: This revi...INTRODUCTION: Neoadjuvant therapy has been proposed as a safe and effective treatment option for resectable colon cancer, providing several advantages over the current standard adjuvant protocol. AREAS COVERED: This review summarizes the recent developments in neoadjuvant strategies for resectable colon cancer, highlighting key clinical trial data, current and emerging challenges, and the role of precision medicine in guiding treatment. Sources for this review were obtained through searches of PubMed, ClinicalTrials.gov, and relevant conference abstracts. EXPERT OPINION: Neoadjuvant therapy is emerging as a promising approach for treating colon cancer, especially for dMMR/MSI-H colon cancer where neoadjuvant immunotherapy have shown exceptional complete pathologic response rates and durable responses. Ongoing trials are focused on identifying optimal treatment approaches that balance oncological efficacy with the minimization of toxicity. A reliable multimodal evaluation framework incorporating advanced staging techniques and biomarkers such as circulating tumor DNA is essential to guide treatment and improve patient selection.
BACKGROUND: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare and highly heterogeneous cytotoxic T-cell lymphoma with unknown epidemiology, clinical features, and prognosis. METHODS: We retrospectively ana...BACKGROUND: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare and highly heterogeneous cytotoxic T-cell lymphoma with unknown epidemiology, clinical features, and prognosis. METHODS: We retrospectively analyzed data on patients with SPTCL from the Surveillance, Epidemiology, and End Results database (2000-2021). Joinpoint plots of incidence were created. Independent prognostic factors for overall survival (OS) and lymphoma-specific survival (LSS) were analyzed using univariate Cox regression analysis. Kaplan - Meier analyses were performed to assess survival. RESULTS: Among 258 included patients, we observed an increase in the overall incidence of SPTCL, particularly among individuals aged ≥ 50. The age at SPTCL onset exhibited a unimodal distribution, with peak incidence in the 60-69-year age group. Multivariate Cox regression analysis indicated that diagnoses made between 2000 and 2006, as well as age ≥ 50, were associated with reduced OS and LSS. We describe a case of primary maxillofacial SPTCL in a pediatric patient at our center. CONCLUSIONS: SPTCL has unique clinical and pathological characteristics and tends to occur in younger patients. Early identification and active treatment are beneficial for improving prognosis and survival.
INTRODUCTION: Breast cancer is one of the most common cancers in women and has a high mortality rate. Current treatment methods, including radiation, chemotherapy, and surgery, have limitations such as surrounding tissue...INTRODUCTION: Breast cancer is one of the most common cancers in women and has a high mortality rate. Current treatment methods, including radiation, chemotherapy, and surgery, have limitations such as surrounding tissue damage and nonspecific toxicity, reducing their effectiveness. As a result, new therapeutic platforms are needed to enhance breast cancer treatment. AREAS COVERED: Nanoparticles, particularly metallic nanoparticles, have shown significant potential in overcoming the limitations of conventional treatments. These nanoparticles offer advantages such as high loading capacity, biocompatibility, adjustable size, and surface modification flexibility, making them ideal for drug delivery. This review focuses on the synthesis of metallic nanoparticles, emphasizing chemical and green synthesis methods. The green synthesis method has gained attention due to its eco-friendliness, biological safety, and cost-effectiveness. Research advancements in biosynthesized metallic nanoparticles for breast cancer therapy are discussed. EXPERT OPINION: The use of bio-synthesized magnetic nanoparticles in the treatment of breast cancer shows promise for both cytotoxicity and targeted medication delivery. By increasing anti-tumor immune responses, their optical and magnetic qualities improve immunotherapy's efficacy. Furthermore, It have the potential to provide potent anticancer treatments and stimulate multidisciplinary research to address current obstacles in the treatment of breast cancer, opening up new therapeutic development pathways.
INTRODUCTION: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality worldwide. Despite advancements in targeted therapies and immune checkpoint inhibitors, many patients with advanced N...INTRODUCTION: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality worldwide. Despite advancements in targeted therapies and immune checkpoint inhibitors, many patients with advanced NSCLC experience disease progression, necessitating novel therapeutic approaches like antibody-drug conjugate (ADC). AREAS COVERED: Sacituzumab govitecan, a trophoblast cell surface antigen 2 (Trop-2) - directed ADC, has emerged as a potential treatment for advanced NSCLC This review evaluates its mechanism of action, clinical efficacy, safety profile, and potential in combination therapies, particularly in heavily pretreated patients. A literature search was conducted using PubMed with keywords 'sacituzumab govitecan' and 'lung cancer,' incorporating relevant studies, including the EVOKE-01 trial. EXPERT OPINION: Sacituzumab govitecan offers a promising alternative for patients unresponsive to conventional treatments. While it demonstrates encouraging response rates and manageable toxicity, further research is needed to refine patient selection and optimize combination strategies. Ongoing trials, such as KEYNOTE-D46/EVOKE-3 May 2001define its role in first-line NSCLC treatment.
INTRODUCTION: CAR-T therapies for relapsed or refractory (r/r) T-cell lymphoblastic leukemia/lymphoma (T-LL/L) faces challenges, with most clinical studies conducted in small, dispersed cohorts and often reviewed alongsi...INTRODUCTION: CAR-T therapies for relapsed or refractory (r/r) T-cell lymphoblastic leukemia/lymphoma (T-LL/L) faces challenges, with most clinical studies conducted in small, dispersed cohorts and often reviewed alongside preclinical studies. This review focuses exclusively on clinical studies, evaluating CAR constructs, safety and efficacy. METHODS: A systematic review was conducted of databases, clinical trial registries, and abstracts from conferences (June 2014 to June 2024). Preclinical studies and studies lacking clinical details were excluded. Data on patient demographics, CAR-T characteristics, response rates, survival, and adverse events were analyzed. RESULTS: Eleven CAR-T constructs targeting CD7 and two targeting CD5 were identified. Complete remission (CR/CRi) rates ranged from 55% to 100%, exceeding 80% in most studies. Relapse, often in extramedullary sites, ranged from 7% to 66%. Cytokine release syndrome and neurotoxicity were generally manageable. GVHD incidence varied (none to 60%), primarily in allogeneic CAR-T recipients. Infections contributed to 6-38% of treatment-related mortality. CONCLUSIONS: CAR-T therapy achieves high response rates in r/r T-LL/L and may serve as a bridge to allogeneic transplantation. However, the short follow-up and the duration of responses remain concerns, and challenges endure, including GVHD, immune recovery and infection control. Standardized reporting is crucial to optimize therapy outcomes and safety in future trials. REGISTRATION: PROSPERO (CRD420251024662).
INTRODUCTION: Breast cancer (BC) prevention in BRCA1/2 mutation carriers remains a significant clinical challenge. Risk-reducing mastectomy (RRM) is the most effective preventive option, lowering BC incidence by over 90%...INTRODUCTION: Breast cancer (BC) prevention in BRCA1/2 mutation carriers remains a significant clinical challenge. Risk-reducing mastectomy (RRM) is the most effective preventive option, lowering BC incidence by over 90%. Despite its survival benefit, the decision to undergo RRM is complex and shaped by psychological, social, and healthcare access factors. AREAS COVERED: This narrative review synthesizes evidence on the oncologic efficacy, safety, and outcomes of RRM in BRCA mutation carriers. Literature was identified through PubMed, Scopus, and Web of Science up to March 2025. Large cohort studies and systematic reviews confirm the effectiveness of RRM. Nipple-sparing mastectomy offers comparable oncologic safety with improved cosmetic and psychological outcomes. Histopathologic analyses frequently reveal occult malignancies, supporting the role of early surgery. However, surgical complications, sensory loss, and sexual health impacts remain important considerations. EXPERT OPINION: RRM is cost-effective, especially when performed at younger ages, but disparities in access to genetic testing and surgery persist. Special populations, such as ovarian cancer survivors and those diagnosed before genetic testing, require individualized care. Advances in risk stratification, surgical techniques, and psychosocial support will enhance outcomes. A multidisciplinary, patient-centered approach is essential for informed decision-making.
Manolitsis I, Kapriniotis K, Katsimperis S
… +8 more, Angelopoulos P, Triantafyllou P, Karagiotis T, Juliebo-Jones P, Mitsogiannis I, Somani B, Skolarikos A, Tzelves L
INTRODUCTION: Muscle-invasive bladder cancer (MIBC) is an aggressive malignancy with high recurrence rates despite standard treatment with radical cystectomy with neoadjuvant chemotherapy. Conventional imaging and histop...INTRODUCTION: Muscle-invasive bladder cancer (MIBC) is an aggressive malignancy with high recurrence rates despite standard treatment with radical cystectomy with neoadjuvant chemotherapy. Conventional imaging and histopathology have limited ability to detect minimal residual disease (MRD) or predict treatment response. Circulating tumor DNA (ctDNA), has emerged as a promising noninvasive biomarker for dynamic tumor monitoring and risk stratification. AREAS COVERED: This review explores the current and emerging applications of ctDNA in MIBC, including its use in neoadjuvant and adjuvant settings, MRD detection, surveillance, and treatment guidance. Key clinical trials, such as IMvigor010/011, ABACUS, NABUCCO, TOMBOLA, MODERN, and VOLGA are discussed, highlighting the prognostic and predictive value of ctDNA across disease stages. Technical and biological limitations are examined, along with challenges related to standardization, cost, and clinical integration. EXPERT OPINION: ctDNA is poised to transform the perioperative management of MIBC by enabling precision-guided treatment decisions. ctDNA assays offer high sensitivity for MRD detection and early relapse prediction. While not yet part of routine clinical practice, ongoing studies will determine whether ctDNA-guided interventions improve patient outcomes. With continued advancements in assay sensitivity, bioinformatics, and integration with radiomic and genomic data, ctDNA is expected to become a cornerstone in the treatment of urothelial carcinoma.
OBJECTIVE: To evaluate the diagnostic accuracy of high b-value diffusion-weighted imaging (DWI) in differentiating malignant from benign breast lesions. METHODS: A comprehensive literature search was conducted across Pub...OBJECTIVE: To evaluate the diagnostic accuracy of high b-value diffusion-weighted imaging (DWI) in differentiating malignant from benign breast lesions. METHODS: A comprehensive literature search was conducted across PubMed, Embase, Cochrane Library, Scopus, and Web of Science for English-language studies on high b-value DWI in breast lesions, from inception to June 2024. Study quality was assessed, and data were extracted. Heterogeneity analysis, forest plots, Deek's funnel plots, and summary receiver operating characteristic (SROC) curves were generated using Stata 16.0 and Meta-Disc 1.4 software. Meta-regression identified sources of heterogeneity. RESULTS: The meta-analysis included 12 studies with 1,747 patients and 1,861 breast lesions (1,000 malignant, 861 benign). Pooled diagnostic metrics were: sensitivity, 0.91 (95% CI: 0.87-0.94); specificity, 0.93 (95% CI: 0.87-0.96); positive likelihood ratio, 12.21 (95% CI: 6.91-21.57); negative likelihood ratio, 0.09 (95% CI: 0.06-0.14); diagnostic odds ratio, 130.75 (95% CI: 56.95-300.21); and AUC, 0.97 (95% CI: 0.95-0.98). CONCLUSION: High b-value DWI has high diagnostic accuracy in differentiating between benign and malignant breast lesions, demonstrating potential as a reliable imaging marker. REGISTRATION: PROSPERO (CRD42024568777).
BACKGROUND: Prostate Cancer (PCa) is a severe disease that affects males globally. The Gleason grading system is a widely recognized method for diagnosing the aggressiveness of PCa using histopathological images. This sy...BACKGROUND: Prostate Cancer (PCa) is a severe disease that affects males globally. The Gleason grading system is a widely recognized method for diagnosing the aggressiveness of PCa using histopathological images. This system evaluates prostate tissue to determine the severity of the disease and guide treatment decisions. However, manual analysis of histopathological images requires highly skilled professionals and is time-consuming. METHODS: To address these challenges, deep learning (DL) is utilized, as it has shown promising results in medical image analysis. Although numerous DL networks have been developed for Gleason grading, many existing methods have limitations such as suboptimal accuracy and high computational complexity. The proposed network integrates MobileNet, an Attention Mechanism (AM), and a capsule network. MobileNet efficiently extracts features from images while addressing computational complexity. The AM focuses on selecting the most relevant features, enhancing the accuracy of Gleason grading. Finally, the capsule network classifies the Gleason grades from histopathological images. RESULTS: The validation of the proposed network used two datasets, PANDA and Gleason-2019. Ablation studies were conducted and evaluated in the proposed architecture. The results highlight the effectiveness of the proposed network. CONCLUSIONS: The proposed network outperformed existing approaches, achieving an accuracy of 98.08% on the PANDA dataset and 97.07% on the Gleason-2019 dataset.
INTRODUCTION: Endoscopic submucosal dissection (ESD) has revolutionized the management of early gastrointestinal (GI) neoplasms by enabling en bloc resection with high R0 rates. Several modifications of conventional ESD...INTRODUCTION: Endoscopic submucosal dissection (ESD) has revolutionized the management of early gastrointestinal (GI) neoplasms by enabling en bloc resection with high R0 rates. Several modifications of conventional ESD (C-ESD) have been introduced, including pocket-creation (PCM-ESD), tunnel (T-ESD), traction-assisted (TA-ESD), and saline immersion therapeutic endoscopy (SITE-ESD) methods. AREAS COVERED: A comprehensive literature search was conducted across main databases through February 2025 using keywords related to ESD, with studies selected based on their relevance. While no single technique has demonstrated superior efficacy and safety across different GI regions, a tailored and integrative approach to different techniques could enhance effectiveness. PCM-ESD and T-ESD are particularly advantageous circumferential lesions in the esophagus and rectum, whereas TA-ESD significantly reduces procedure time, particularly in colonic lesions. Moreover, PCM-ESD has demonstrated higher effectiveness for colorectal lesions compared to C-ESD. SITE-ESD has shown benefits in colorectal resections by improving trimming, submucosal space visualization and coagulation control.Advanced traction systems and resection tools has optimized ESD performance. However, selecting the most appropriate approach requires careful consideration of lesion characteristics (particularly fibrosis and location). EXPERT OPINION: While conventional ESD remains the foundation, TA and SITE are expected to become the preferred approach in select GI regions during the following years.
Ingrosso G, Lancia A, Bardoscia L
… +17 more, Becherini C, Bottero M, Bertini N, Cai T, Caini S, Caserta C, Doccioli C, Festa E, Francolini G, Giacomelli I, Paolieri F, Scartoni D, Pisani AR, Bellavita R, Livi L, Aristei C, Detti B
INTRODUCTION: de novo low-volume metastatic hormone-sensitive prostate cancer (mHSPC) patients are characterized by a limited number of metastases at diagnosis. Intensifying the current diagnostic and therapeutic approac...INTRODUCTION: de novo low-volume metastatic hormone-sensitive prostate cancer (mHSPC) patients are characterized by a limited number of metastases at diagnosis. Intensifying the current diagnostic and therapeutic approach including multimodality therapy seems to be key in the clinical management of such patients. AREAS COVERED: We comprehensively review the current staging and treatment options for de novo low-volume mHSPC. EXPERT OPINION: PSMA-PET should be used in staging high-risk prostate cancer to detect metastatic disease and better stratify patients for individualized treatment. In the era of Androgen Receptor Pathway Inhibitors (ARPIs), Androgen Deprivation Therapy (ADT) alone should be considered an undertreatment for the majority of the patients. Based on current data in the literature, the most effective therapeutic strategy seems to be the combination of intensified systemic treatment (including ADT + ARPI) and radiotherapy for the primary tumor. The role of cytoreductive radical prostatectomy is currently being investigated as well as metastasis-directed therapy to metastatic sites.
INTRODUCTION: Breast cancer remains a significant global health issue. Despite advances in detection and treatment, its complexity is driven by genetic, environmental, and structural factors. Computational methods like F...INTRODUCTION: Breast cancer remains a significant global health issue. Despite advances in detection and treatment, its complexity is driven by genetic, environmental, and structural factors. Computational methods like Finite Element Modeling (FEM) have transformed our understanding of breast cancer risk and progression. AREAS COVERED: Advanced computational approaches in breast cancer research are the focus, with an emphasis on FEM's role in simulating breast tissue mechanics and enhancing precision in therapies such as radiofrequency ablation (RFA). Machine learning (ML), particularly Convolutional Neural Networks (CNNs), has revolutionized imaging modalities like mammograms and MRIs, improving diagnostic accuracy and early detection. AI applications in analyzing histopathological images have advanced tumor classification and grading, offering consistency and reducing inter-observer variability. Explainability tools like Grad-CAM, SHAP, and LIME enhance the transparency of AI-driven models, facilitating their integration into clinical workflows. EXPERT OPINION: Integrating FEM and ML represents a paradigm shift in breast cancer management. FEM offers precise modeling of tissue mechanics, while ML excels in predictive analytics and image analysis. Despite challenges such as data variability and limited standardization, synergizing these approaches promises adaptive, personalized care. These computational methods have the potential to redefine diagnostics, optimize treatment, and improve patient outcomes.
BACKGROUND: The optimal criteria for lateral lymph node dissection (LLND) in rectal cancer following neoadjuvant therapy remain undefined. This systematic review and meta-analysis evaluated the diagnostic accuracy of lat...BACKGROUND: The optimal criteria for lateral lymph node dissection (LLND) in rectal cancer following neoadjuvant therapy remain undefined. This systematic review and meta-analysis evaluated the diagnostic accuracy of lateral lymph node metastasis (LLNM) to refine criteria for selective LLND. RESEARCH DESIGN AND METHODS: A systematic search of PubMed, Embase, and the Cochrane Library (10 August 2024) identified studies assessing magnetic resonance imaging (MRI)-based LLNM detection in patients with rectal cancer who underwent neoadjuvant therapy and radical surgery. Studies reporting MRI-based LLNM assessments with pathological confirmation were included. Non-English studies, reviews, case reports, and those lacking lymph node size data were excluded. The risk of bias was assessed using QUADAS-2. Pooled sensitivity, specificity, and diagnostic odds ratios were estimated using hierarchical summary receiver operating characteristic curve (HSROC) analysis. RESULTS: Eleven studies met the inclusion criteria. All used MRI-based size assessments. The pooled sensitivity and specificity were 0.776 (95% CI: 0.639-0.872) and 0.694 (95% CI: 0.541-0.813), respectively, with an HSROC area under the curve (AUC) of 0.801. CONCLUSIONS: MRI is the most widely used modality for diagnosing LLNM in rectal cancer patients who have undergone neoadjuvant therapy, with size criteria being the most commonly applied. REGISTRATION: PROSPERO (CRD42024578499).
Hotchandani H, Sengar M, Shetty A
… +13 more, John A, Karulkar A, Kalra D, Ravikumar S, Jaiswal A, Yadav Y, Parkar S, Walawalkar A, Kadam S, Bagal B, Nayak L, Purwar R, Jain H
INTRODUCTION: CAR-T cell therapy has changed the treatment paradigm for hematological malignancies, offering a curative potential for patients with relapsed or refractory disease. India, with its significant burden of he...INTRODUCTION: CAR-T cell therapy has changed the treatment paradigm for hematological malignancies, offering a curative potential for patients with relapsed or refractory disease. India, with its significant burden of hematological malignancies, faces unique challenges in implementing this therapy. The development of indigenous CAR-T cells has reduced costs substantially, but barriers remain, including limited manufacturing capacity, relatively high costs, and logistical constraints. AREAS COVERED: This article emphasizes the importance of optimized patient selection and triaging of apheresis slots to maximize the benefits of CAR-T cell therapy. The use of efficient bridging therapies and antibody-based approaches are being explored to improve outcomes, particularly in aggressive lymphomas and leukemias. Opportunities lie in leveraging India's growing biotechnology sector for cost-efficient production and in evaluating novel combination therapies to enhance CAR-T cell efficacy. This article also explores the technical and socioeconomic challenges of CAR-T cell development in India and suggests strategies to enhance accessibility, affordability, and implementation. EXPERT OPINION: Ongoing advancements and research may help tailor CAR-T cell protocols to the local population. Future integration of NK cell therapy, TCR-based approaches, and multi-antigen targeting holds promise for enhancing therapeutic efficacy.
INTRODUCTION: Cervical cancer is still a major global health threat, specifically in countries with little access to health services. Angiogenesis in cervical cancer not only contributes to tumor growth, metastasis, and...INTRODUCTION: Cervical cancer is still a major global health threat, specifically in countries with little access to health services. Angiogenesis in cervical cancer not only contributes to tumor growth, metastasis, and resistance to therapy but also serves as a therapeutic target itself. This gives hope for the possible therapy. AREAS COVERED: This review covers key molecular mechanisms in cervical cancer, including VEGF/VEGFR, HIF-1α, and PI3K/Akt pathways. It also discusses anti-angiogenic therapies like bevacizumab, small-molecule compounds, and emerging approaches such as nanoparticle-based drug delivery. Emphasis is placed on angiogenesis-related biomarkers for diagnosis and treatment selection, stressing the need for affordable therapies in low-resource settings. A literature search was conducted using PubMed, Scopus, and Google Scholar up to March 2025, focusing on VEGF/VEGFR signaling, anti-angiogenic therapies, and resistance mechanisms in cervical cancer. EXPERT OPINION: Despite promise, resistance, toxicity, and cost remain major challenges for anti-angiogenic therapy's clinical use. Combination strategies with immunotherapy, chemotherapy, and targeted agents may be more effective. Precision medicine using multi-omics and AI offers hope for better outcomes. Future studies should evaluate drug combinations with synergistic effects and develop management strategies to universalize innovative treatments.
INTRODUCTION: Vitamins are essential for homeostasis and proper functioning of organisms. These micronutrients prevent tumor onset by functioning as antioxidants and enzymatic cofactors involved in anti-stress and immune...INTRODUCTION: Vitamins are essential for homeostasis and proper functioning of organisms. These micronutrients prevent tumor onset by functioning as antioxidants and enzymatic cofactors involved in anti-stress and immune responses, modulating epigenetic regulators, and shaping the microbiota composition. Unbalanced diets and sedentary lifestyles contribute to obesity, associated with increasing cancer risk. Cancer patients often exhibit vitamin deficiencies due to chronic inflammation, anticancer therapies, and tumor-induced metabolic changes, leading to malnutrition and cachexia. AREAS COVERED: This review critically analyzes preclinical and clinical studies, sourced from PubMed and ClinicalTrials.gov databases, that investigate the potential benefits of vitamin supplementation and dietary interventions, such as intermittent fasting and ketogenic diets, in mouse tumor models and cancer patients. This analysis elucidates the limitations of such interventions and suggests optimal dietary strategies to prevent cancer and enhance patients' quality of life and prognosis. EXPERT OPINION: To date, clinical studies have found no substantial benefit of over-the-counter vitamin supplements and dietary interventions on cancer patients' health and prognosis. To prevent the spread of useless and potentially harmful products by the nutraceutical industry, establishing a regulatory authority is necessary to monitor and ensure product quality and validity before commercialization.
INTRODUCTION: Although basal cell carcinomas (BCC) are the most common skin cancer and usually considered as 'easy-to-treat,' locally advanced BCC (laBCC) and metastatic BCC (mBCC) are rather exceptional and often more '...INTRODUCTION: Although basal cell carcinomas (BCC) are the most common skin cancer and usually considered as 'easy-to-treat,' locally advanced BCC (laBCC) and metastatic BCC (mBCC) are rather exceptional and often more 'difficult-to-treat.' They load a high burden on the quality of life (QoL) of the patients, often elderly and frail individuals. Several management options are possible, varying from supportive therapy without any therapeutic intervention until anti-programmed cell death protein-1 (PD-1) immunotherapy, such as cemiplimab, either administered intravenously or intralesional. In between this spectrum, oral hedgehog inhibitors including vismodegib and sonidegib, electrochemotherapy, different types of radiotherapy, and surgery can be considered. CAR-T cell therapy, anti-LAG therapy, and multiple combination therapies are currently under investigation for laBCC and mBCC. AREAS COVERED: Current and future treatment options for the management of laBCC and mBCC, limitations of different approaches as well as some practical and financial aspects are presented. EXPERT OPINION: The management of laBCC and mBCC patients is determined by a multidisciplinary dermato-oncology board, including dermatologists, medical oncologists, radiotherapists, pathologists, and surgeons, as well as the patient's GP. Today, experts recommend keeping as long as possible laBCC and mBCC patients under sequential courses of HHIs, if surgery and/or radiotherapy are not amenable.
INTRODUCTION: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibition in combination with endocrine therapy is the mainstay of treatment for hormone receptor-positive, HER2-negative (HR + /HER2-) advanced breast cancer; th...INTRODUCTION: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibition in combination with endocrine therapy is the mainstay of treatment for hormone receptor-positive, HER2-negative (HR + /HER2-) advanced breast cancer; the CDK4/6 inhibitors abemaciclib and ribociclib are also approved for high-risk, early-stage, HR + /HER2- breast cancer. Numerous studies exploring CDK4/6 inhibitors in the early-stage setting are ongoing, as well as many more exploring novel combinations in the metastatic setting. AREAS COVERED: Here, we review the basis of CDK4/6 inhibition for HR +/HER2- breast cancer, the pivotal clinical trials which led to regulatory approval, and ongoing trials evaluating novel combinations to further improve outcomes for those with both early and advanced HR+/HER2- breast cancer. Current literature was reviewed by a comprehensive search of PubMed MEDLINE (1/1/2000-12/31/2024). EXPERT OPINION: CDK4/6 inhibitors are integral in the management of both advanced and high-risk, early-stage HR + /HER2- breast cancer. Biomarkers predictive of CDK 4/6 inhibitor (CDK4/6i) benefit remain elusive, and clinical and pathological features remain key to identifying those who are candidates for CDK4/6 inhibition in the early-stage setting. Numerous trials evaluating the role of a CDK4/6i with novel endocrine therapy partners and other targeted agents are ongoing, with the goal of improving outcomes for those with HR + /HER2- disease.