Therapy For Treatment Of Cancer Research Articles

Photo-Activated Oxidative Stress Amplifier: A Strategy for Targeting Glutathione Metabolism and Enhancing ROS-Mediated Therapy in Triple-Negative Breast Cancer Treatment.

Amplifying oxidative stress within tumor cells can effectively inhibit the growth and metastasis of triple-negative breast cancer (TNBC). Therefore, the development of innovative nanomedicines that can effectively disrupt the redox balance represents a promising yet challenging therapeutic strategy for TNBC. In this study, an oxidative stress amplifier, denoted as PBCH, comprising PdAg mesoporous nanozyme and a CaP mineralized layer, loaded with GSH inhibitor L-buthionine sulfoximine (BSO), and further surface-modified with hyaluronic acid that can target CD44, is introduced. In the acidic tumor microenvironment, Ca2+ is initially released, thereby leading to mitochondrial dysfunction and eventually triggering apoptosis. Additionally, BSO suppresses the synthesis of intracellular reduced GSH and further amplifies the level of oxidative stress in cancer cells. Furthermore, PdAg nanozyme can be activated by near-infrared light to induce photothermal and photodynamic effects, causing a burst of ROS and simultaneously promoting cell apoptosis via provoking immunogenic cell death. The high-performance therapeutic effects of PBCH, based on the synergistic effect of aforementioned multiple oxidative damage and photothermal ablation, are validated in TNBC cells and animal models, declaring its potential as a safe and effective anti-tumor agent. The proposed approach offers new perspectives for precise and efficient treatment of TNBC.

Insights Into the Patient Experience of Hormone Therapy for Early Breast Cancer Treatment Using Patient Forum Discussions and Natural Language Processing.

Understanding the real-world experience of patients with early breast cancer (eBC) is imperative for optimizing outcomes and evolving patient care. However, there is a lack of patient-level data, hindering clinical development. This social listening study was performed to understand patient insights into symptoms and impacts of hormone therapy (HT) for eBC using posts from patient forums on breastcancer.org to inform future clinical research. Natural language processing (NLP) and machine learning techniques were used to identify themes related to eBC from a sample of 500,000 posts. After relevant data selection, 362,074 eBC posts were retained for further analysis of symptoms and impacts related to HT, as well as insights into symptom severity, pain locations, and symptom management using exercise and yoga. Overall, 32 symptoms and nine impacts had significant associations with ≥one HT. Hot flush (relative risk [RR], 6.70 [95% CI, 3.36 to 13.36]), arthralgia (RR, 6.67 [95% CI, 3.53 to 12.59]), weight increased (RR, 4.83 [95% CI, 3.20 to 7.28]), mood swings (RR, 7.36 [95% CI, 5.75 to 9.42]), insomnia (RR, 4.76 [95% CI, 3.14 to 7.22]), and depression (RR, 3.05 [95% CI, 1.71 to 5.44]) demonstrated the strongest associations. Severe headache, dizziness, back pain, and muscle spasms showed significant associations with ≥one HT despite their low overall prevalence in eBC posts. The social listening approach allowed the identification of real-world insights from posts specific to eBC HT from a large-scale online breast cancer forum that captured experiences from a uniquely diverse group of patients. Using NLP has a potential to scale analysis of patient feedback and reveal actionable insights into patient experiences of treatment that can inform the development of future therapies and improve the care of patients with eBC.

Cationic conjugated polymer coupled non-conjugated segments for dually enhanced NIR-II fluorescence and lower-temperature photothermal-gas therapy

The lack of a simple design strategy to obtain ideal conjugated polymers (CPs) with high absorbance and fluorescence (FL) in the near-infrared-II (NIR-II; 1000–1700 nm) region still hampers the success of NIR-II light-triggered phototheranostics. Herein, novel phototheranostic nanoparticles (PPN-NO NPs) were successfully prepared by coloading a cationic NIR-II CPs (PBC-co-PBF-NMe3) and a NO donor (S-nitroso-N-acetylpenicillamine, SNAP) onto a 1:1 mixture of DSPE-PEG5000 and dimyristoylphosphatidylcholine (DMPC) for NIR-II FL and NIR-II photoacoustic (PA) imaging-guided low-temperature NIR-II photothermal therapy (PTT) and gas combination therapy for cancer treatment. A precise NIR-II FL dually enhanced design tactic was proposed herein by integrating flexible nonconjugated segments (C6) into the CPs backbone and incorporating quaternary ammonium salt cationic units into the CPs side chain, which considerably increased the radiative decay pathway, resulting in desirable NIR-II FL intensity and balanced NIR-II absorption and NIR PTT properties. The phototheranostic PPN-NO NPs exhibited distinguished NIR-II FL and PA imaging performance in tumor-bearing mice models. Furthermore, the low-temperature photothermal effect of PPN-NO NPs could initiate NO release upon 980 nm laser irradiation, efficiently suppressing tumor growth owing to the combination of low-temperature NIR-II PTT and NO gas therapy in vitro and in vivo.Graphical

Carbon - 12C ion radiation-induced cell death and molecular mechanisms in malignant cells: Evidence from in vivo and in vitro

Conventional radiotherapy has been revolutionized for several decades. Recently, the delivery of high linear energy transfer (LET) radiation such as heavy carbon ion therapy has gained more attention. Among all low-energy therapies such as photon, X-ray, and gamma radiation therapy, 12C heavy carbon ion therapy is the best therapy for cancer treatment due to its high relative biological effectiveness (RBE). It has been studied that many tumors show resistance to chemotherapy and low energy transfer radiation. The unique nature of high LET shows unique Bragg peaks where very little radiation are applied on the tumor cells and better results can be achieved. It effectively kills the tumor cells without affecting the normal cells. There are some limitations to conventional radiotherapy. Radiotherapy with the low LET group may not work properly. Carbon ion radiation (CIR) induces malignant cell death in different modes, such as apoptosis, senescence, autophagy, immunogenic cell death and necrosis. Heavy carbon ion therapy enhances cell death by altering different molecular signalling pathways such as p53, AKT, MEK, caspase and STAT–3. Investigation of the major molecular cell death by carbon ion irradiation is very essential to understand the modalities of heavy carbon ion induced cell death. In this context, the investigation of different signaling cascades may open new horizons in cancer treatment. The therapeutic efficacy and application of heavy carbon ion beams along with some molecular inhibitors, radio sensitizers, and gene therapy would be helpful for future cancer treatment. Therefore, a more thorough investigation in this field is needed. The current review article highlights the recent advances in cancer therapy research based on Carbon 12C Ion radiation-induced cell death.

Emerging immune checkpoint and its combination therapy in cancer treatment

Emerging immune checkpoint and its combination therapy in cancer treatment

Neoadjuvant immunotherapy ushers in a new era of gastric cancer treatment

Recent advances in tumor immunology have made immunotherapy a new direction for neoadjuvant treatment of gastric cancer. Multiple clinical trials have confirmed that combining immunotherapy with chemotherapy and targeted therapy in the neoadjuvant treatment of gastric cancer can effectively improve treatment response and prolong patient survival time. This article aims to comment on the application of immunotherapy in the neoadjuvant treatment of gastric cancer, exploring its mechanisms, integration strategies with traditional treatments, safety, and personalized precision therapy in the hope of providing new insights and directions for the field of gastric cancer treatment.

Postbiotics as Adjuvant Therapy in Cancer Care

Postbiotics are defined as a preparation of inanimate microorganisms and/or their components that confers a health benefit to the host. They range from cell wall fragments to metabolites, bacterial lysates, extracellular vesicles, and short-chain fatty acids (SCFAs). Postbiotics may influence carcinogenesis via a variety of mechanisms. They can promote homeostatic immune responses, reduce inflammation, induce selective cytotoxicity against tumor cells, as well as the enabling the control of tumor cell proliferation and enhancing intestinal epithelial barrier function. Therefore, probiotics can serve as an adjunct strategy in anticancer treatment together with chemotherapy and immunotherapy. Up to now, the only relevant postbiotics used as interventions in oncological patients remain vitamin K molecules, with few phase-II and III trials available. In fact, postbiotics’ levels are strictly dependent on the gut microbiota’s composition, which may vary between individuals and can be altered under different physiological and pathological conditions. Therefore, the lack of consistent clinical evidence supporting postbiotics’ efficacy is due to their poor bioavailability, short half-life, and fluctuating levels. Synbiotics, a mixture of prebiotics and probiotics, are expected to have a more homogeneous bioavailability with respect to postbiotics and may have greater potential for future development. In this review, we focus on the role of postbiotics as an adjuvant therapy in cancer treatment.

Novel Directed Enzyme Prodrug Therapy for Cancer Treatment Based on 2′-Deoxyribosyltransferase-Conjugated Magnetic Nanoparticles

Directed enzyme prodrug therapy (DEPT) strategies show promise in mitigating chemotherapy side effects during cancer treatment. Among these, the use of immobilized enzymes on solid matrices as prodrug activating agents (IDEPT) presents a compelling delivery strategy, offering enhanced tumor targeting and reduced toxicity. Herein, we report a novel IDEPT strategy by employing a His-tagged Leishmania mexicana type I 2′-deoxyribosyltransferase (His-LmPDT) covalently attached to glutaraldehyde-activated magnetic iron oxide nanoparticles (MIONPs). Among the resulting derivatives, PDT-MIONP3 displayed the most favorable catalyst load/retained activity ratio, prompting its selection for further investigation. Substrate specificity studies demonstrated that PDT-MIONP3 effectively hydrolyzed a diverse array of 6-oxo and/or 6-amino purine 2′-deoxynucleosides, including 2-fluoro-2′-deoxyadenosine (dFAdo) and 6-methylpurine-2′-deoxyribose (d6MetPRib), both well-known prodrugs commonly used in DEPT. The biophysical characterization of both MIONPs and PDT-MIONPs was conducted by TEM, DLS, and single particle ICPMS techniques, showing an ideal nanosized range and a zeta potential value of −47.9 mV and −78.2 mV for MIONPs and PDT-MIONPs, respectively. The intracellular uptake of MIONPs and PDT-MIONPs was also determined by TEM and single particle ICPMS on HeLa cancer cell lines and NIH3T3 normal cell lines, showing a higher intracellular uptake in tumor cells. Finally, the selectivity of the PDT-MIONP/dFAdo IDEPT system was tested on HeLa cells (24 h, 10 µM dFAdo), resulting in a significant reduction in tumoral cell survival (11% of viability). Based on the experimental results, PDT-MIONP/dFAdo presents a novel and alternative IDEPT strategy, providing a promising avenue for cancer treatment.

A Nanoencapsulated Ir(III)-Phthalocyanine Conjugate as a Promising Photodynamic Therapy Anticancer Agent.

Despite the potential of photodynamic therapy (PDT) in cancer treatment, the development of efficient and photostable photosensitizing molecules that operate at long wavelengths of light has become a major hurdle. Here, we report for the first time an Ir(III)-phthalocyanine conjugate (Ir-ZnPc) as a novel photosensitizer for high-efficiency synergistic PDT treatment that takes advantage of the long-wavelength excitation and near infrared (NIR) emission of the phthalocyanine scaffold and the known photostability and high phototoxicity of cyclometalated Ir(III) complexes. In order to increase water solubility and cell membrane permeability, the conjugate and parent zinc phthalocyanine (ZnPc) were encapsulated in amphoteric redox-responsive polyurethane-polyurea hybrid nanocapsules (Ir-ZnPc-NCs and ZnPc-NCs, respectively). Photobiological evaluations revealed that the encapsulated Ir-ZnPc conjugate achieved high photocytotoxicity in both normoxic and hypoxic conditions under 630 nm light irradiation, which can be attributed to dual Type I and Type II reactive oxygen species (ROS) photogeneration. Interestingly, PDT treatments with Ir-ZnPc-NCs and ZnPc-NCs significantly inhibited the growth of three-dimensional (3D) multicellular tumor spheroids. Overall, the nanoencapsulation of Zn phthalocyanines conjugated to cyclometalated Ir(III) complexes provides a new strategy for obtaining photostable and biocompatible red-light-activated nano-PDT agents with efficient performance under challenging hypoxic environments, thus offering new therapeutic opportunities for cancer treatment.

Transforming Cell-Drug Interaction through Granular Hydrogel-Mediated Delivery of Polyplex Nanoparticles for Enhanced Safety and Extended Efficacy in Gene Therapy.

The utilization of hydrogels for DNA/cationic polymer polyplex nanoparticle (polyplex) delivery has significantly advanced gene therapy in tissue regeneration and cancer treatment. However, persistent challenges related to the efficacy and safety of encapsulated polyplexes, stemming from issues such as aggregation, degradation, or difficulties in controlled release during or postintegration with hydrogel scaffolds, necessitate further exploration. Here, we introduce an injectable gene therapy gel achieved by incorporating concentrated polyplexes onto densely packed hydrogel microparticles (HMPs). Polyplexes, when uniformly adhered to the gene therapy gel through reversible electrostatic interactions, can detach from the HMP surface in a controlled manner, contrasting with free polyplexes, and thereby reducing dose-dependent toxicity during transfection. Additionally, the integration of RGD cell adhesion peptides enhances the scaffolding characteristics of the gel, facilitating cell adhesion, migration, and further minimizing toxicity during gene drug administration. Notably, despite the overall transfection efficiency showing average performance, utilizing confocal microscopy to meticulously observe and analyze the cellular states infiltrating into various depths of the gene therapy gel resulted in the groundbreaking discovery of significantly enhanced local transfection efficiency, with primary cell transfection approaching 80%. This phenomenon could be potentially attributed to the granular hydrogel-mediated delivery of polyplex nanoparticles, which revolutionizes the spatial and temporal distribution and thus the "encounter" mode between polyplexes and cells. Moreover, the gene therapy gel's intrinsic injectability and self-healing properties offer ease of administration, making it a highly promising candidate as a novel gene transfection gel dressing with significant potential across various fields, including regenerative medicine and innovative living materials.

Therapeutic Applications of Rosmarinic Acid in Cancer-Chemotherapy-Associated Resistance and Toxicity.

Chemotherapeutic drugs and radiotherapy are fundamental treatments to combat cancer, but, often, the doses in these treatments are restricted by their non-selective toxicities, which affect healthy tissues surrounding tumors. On the other hand, drug resistance is recognized as the main cause of chemotherapeutic treatment failure. Rosmarinic acid (RA) is a polyphenol of the phenylpropanoid family that is widely distributed in plants and vegetables, including medicinal aromatic herbs, consumption of which has demonstrated beneficial activities as antioxidants and anti-inflammatories and reduced the risks of cancers. Recently, several studies have shown that RA is able to reverse cancer resistance to first-line chemotherapeutics, as well as play a protective role against toxicity induced by chemotherapy and radiotherapy, mainly due to its scavenger capacity. This review compiles information from 56 articles from Google Scholar, PubMed, and ClinicalTrials.gov aimed at addressing the role of RA as a complementary therapy in cancer treatment.

Supramolecular self-sensitized dual-drug nanoassemblies potentiating chemo-photodynamic therapy for effective cancer treatment

Chemo-photodynamic synergistic therapy (CPST) holds tremendous promise for treating cancers. Unfortunately, existing CPST applications suffer from complex synthetic procedures, low drug co-loading efficiency, and carrier-related toxicity. To address these issues, we have developed a supramolecular carrier-free self-sensitized nanoassemblies by co-assembling podophyllotoxin (PTOX) and chlorin e6 (Ce6) to enhance CPST efficiency against tumors. The nanoassemblies show stable co-assembly performance in simulative vivo neural environment (∼150 nm), with high co-loading ability for PTOX (72.2 wt%) and Ce6 (27.8 wt%). In vivo, the nanoassemblies demonstrate a remarkable ability to accumulate at tumor sites by leveraging the enhanced permeability and retention (EPR) effect. The disintegration of nanoassemblies following photosensitizer bioactivation triggered by the acidic tumor environment effectively resolves the challenge of aggregation-caused quenching (ACQ) effect. Upon exposure to external light stimulation, the disintegrated nanoassemblies not only illuminate cancer cells synergistically but also exert a more potent antitumor effect when compared with PTOX and Ce6 administered alone. This self-sensitized strategy represents a significant step forward in CPST, offering a unique co-delivery paradigm for clinic cancer treatment.

H2O2 Photosynthesis from H2O and O2 under Weak Light by Carbon Nitrides with the Piezoelectric Effect.

Driven by the essential need of a green, safe, and low-cost approach to producing H2O2, a highly valuable multifunctional chemical, artificial photosynthesis emerges as a promising avenue. However, current catalyst systems remain challenging, due to the need of high-density sunlight, poor selectivity and activity, or/and unfavorable thermodynamics. Here, we reported that an indirect 2e- water oxidation reaction (WOR) in photocatalytic H2O2 production was unusually activated by C5N2 with piezoelectric effects. Interestingly, under ultrasonication, C5N2 exhibited an overall H2O2 photosynthesis rate of 918.4 μM/h and an exceptionally high solar-to-chemical conversion efficiency of 2.6% after calibration under weak light (0.1 sun). Mechanism studies showed that the piezoelectric effect of carbon nitride overcame the high uphill thermodynamics of *OH intermediate generation, which enabled a new pathway for 2e- WOR, the kinetic limiting step in the overall H2O2 production from H2O and O2. Benefiting from the outstanding sonication-assisted photocatalytic H2O2 generation under weak light, the concept was further successfully adapted to biomedical applications in efficient sono-photochemodynamic therapy for cancer treatment and water purification.

Biodegradable Ruthenium-Rhenium Complexes Containing Nanoamplifiers: Triggering ROS-Induced CO Release for Synergistic Cancer Treatment.

The constrained effectiveness of photodynamic therapy (PDT) has impeded its widespread use in clinical practice. Urgent efforts are needed to address the shortcomings faced in photodynamic therapy, such as photosensitizer toxicity, short half-life, and limited action range of reactive oxygen species (ROS). In this study, a biodegradable copolymer nanoamplifier is reported that contains ruthenium complex (Ru-complex) as photosensitizer (PS) and rhenium complex (Re-complex) as carbon monoxide (CO)-release molecule (CORM). The well-designed nanoamplifier brings PS and CORM into close spatial proximity, significantly promotes the utilization of light-stimulated reactive oxygen species (ROS), and cascaded amplifying CO release, thus enabling an enhanced synergistic effect of PDT and gas therapy for cancer treatment. Moreover, owing to its intrinsic photodegradable nature, the nanoamplifier exhibits good tumor accumulation and penetration ability, and excellent biocompatibility in vivo. These findings suggest that the biodegradable cascaded nanoamplifiers pave the way for a synergistic and clinically viable integration of photodynamic and gas therapy.

Surface Engineering Enhances Vanadium Carbide MXene-Based Nanoplatform Triggered by NIR-II for Cancer Theranostics.

Despite the advantages of high tissue penetration depth, selectivity, and non-invasiveness of photothermal therapy for cancer treatment, developing NIR-II photothermal agents with desirable photothermal performance and advanced theranostics ability remains a key challenge. Herein, a universal surface modification strategy is proposed to effectively improve the photothermal performance of vanadium carbide MXene nanosheets (L-V2C) with the removal of surface impurity ions and generation of mesopores. Subsequently, MnOx coating capable of T1-weighted magnetic resonance imaging can be in situ formed through surface redox reaction on L-V2C, and then, stable nanoplatforms (LVM-PEG) under physiological conditions can be obtained after further PEGylation. In the tumor microenvironment irradiated by NIR-II laser, multivalent Mn ions released from LVM-PEG, as a reversible electronic station, can consume the overexpression of glutathione and catalyze a Fenton-like reaction to produce ·OH, resulting in synchronous cellular oxidative damage. Efficient synergistic therapy promotes immunogenic cell death, improving tumor-related immune microenvironment and immunomodulation, and thus, LVM-PEG can demonstrate high accuracy and excellent anticancer efficiency guided by multimodal imaging. As a result, this study provides a new approach for the customization of 2D surface strategies and the study of synergistic therapy mechanisms, highlighting the application of MXene-based materials in the biomedical field.

Oral administration of oligo fucoidan improves the survival rate, quality of life, and immunity in patients with lung cancer.

Lung cancer, the most commonly diagnosed cancer globally, has the highest incidence and mortality rates in Taiwan. It can be divided into two types. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancers, which is further divided into adenocarcinoma, squamous cell carcinoma, and large cell lung cancer accounting for approximately 40%, 25%, and 15% of NSCLC cases, respectively. Small cell lung cancer accounts for approximately 15% of lung cancers. Early systemic therapy NSCLC was based on chemotherapy, and immunotherapy is currently under development. Fucoidan, from brown seaweed extracts, shows promise in mitigating radiation-induced lung fibrosis in animal studies, suggesting its potential as an adjuvant for radiation therapy-related lung fibrosis in lung cancer patients. However, the clinical utility of such adjuvant therapy in lung cancer treatment remains uncertain. The purpose of this study was to investigate the effects of oral administration of oligo-fucoidan on the survival rate, quality of life, and immunity of patients with lung cancer. Subjects with Non-small cell lung cancer aged between 20 and 80 were collected from outpatient clinics, divided into control group (n = 7): conventional therapy and fucoidan group (n = 13): received conventional therapy+ oral supplementation of oligo-fucoidan (550 mg × 4 tablets). Data were collected before the study, at weeks 4, 12, and 24 during the study, and to collect 20 ml of peripheral blood, for analysis biochemical data, liver and kidney function, lymphocyte population, inflammation cytokines, and using EORTC QLQ-C30 questionnaire to assess quality of life. The survival rates of the subjects in the control and fucoidan groups were 20% and 28.6%, respectively. During the study, patients in the fucoidan group experienced a better quality of life than those in the control group, but this difference lacked statistical significance. Oligo-fucoidan increases the CD19 lymphocyte population. The patients in the fucoidan group also had Lower inflammatory cytokine. Oligo-fucoidan holds promise as an adjuvant therapy to enhance the survival rate, quality of life, and immune function in patients with lung cancer.

Modifications of Nanobubble Therapy for Cancer Treatment.

Cancer development is related to genetic mutations in primary cells, where 5-10% of all cancers are derived from acquired genetic defects, most of which are a consequence of the environment and lifestyle. As it turns out, over half of cancer deaths are due to the generation of drug resistance. The local delivery of chemotherapeutic drugs may reduce their toxicity by increasing their therapeutic dose at targeted sites and by decreasing the plasma levels of circulating drugs. Nanobubbles have attracted much attention as an effective drug distribution system due to their non-invasiveness and targetability. This review aims to present the characteristics of nanobubble systems and their efficacy within the biomedical field with special emphasis on cancer treatment. In vivo and in vitro studies on cancer confirm nanobubbles' ability and good blood capillary perfusion; however, there is a need to define their safety and side effects in clinical trials.

Synthesis and characterization of chitosan mediated gold nanoparticles for sensitization of cancer cells

The report focuses on the preparation of chitosan mediated gold nanoparticles (Au@CS NPs) and theirapplication in radiotherapy. It highlights the use of gold nanoparticles as a way to enhance the efficacy of radiation therapy in cancer treatment. The process of fabrication of these gold nanoparticles using CS as both a stabilizing and reducing agent is detailed. CS, a biopolymer derived from chitin, is considered biocompatible and biodegradable and has been used largely in biomedicine. The properties of gold nanoparticles stabilized by CS were analyzed using various techniques such as FESEM, STEM, DLS, zeta potential, and UV–Vis. Finally, the in vitro assays were conducted to study the radioenhancement effect of Au@CS NPs on breast cancer cell line (4T1) as a radiosensitizer agent through the cell viability and reactive oxygen species (ROS) generation assays. The results show that Au@CS NPs could produce ROS within cancer cells and enhance sensitization of cancer cells against X‐ray.

Prognostic impact of selection criteria of current adjuvant endocrine therapy trials NATALEE and monarchE in postmenopausal HRpos/HER2neg breast cancer patients treated with upfront letrozole

BackgroundThe monarchE and NATALEE trials demonstrated the benefit of CDK4/6 inhibitor (CDK4/6i) therapy in adjuvant breast cancer (BC) treatment. Patient selection, based on clinical characteristics, delineated those at high (monarchE) and high/intermediate recurrence risk (NATALEE). This study employed a historical patient cohort to describe the proportion and prognosis of patients eligible for adjuvant CDK4/6i trials. MethodsBetween 2009 and 2011, 3529 patients were enrolled in the adjuvant PreFace clinical trial (NCT01908556). Eligibility criteria included postmenopausal patients with hormone receptor-positive (HRpos) BC for whom a five-year upfront therapy with letrozole was indicated. Patients were categorized into prognostic groups according to monarchE and NATALEE inclusion criteria, and their invasive disease-free survival (iDFS) and overall survival (OS) were assessed. ResultsAmong 2891 HRpos patients, 384 (13.3%) met the primary monarchE inclusion criteria. The majority (n=261) qualified due to having ≥4 positive lymph nodes. For NATALEE, 915 out of 2886 patients (31.7%) met the eligibility criteria, with 126 patients (13.7%) being node-negative. Patients from monarchE with ≥4 positive lymph nodes and NATALEE with stage III BC exhibited the poorest prognosis (3-year iDFS rate 0.87). Patients ineligible for the trials demonstrated prognoses similar to the most favorable patient groups within the eligibility criteria. ConclusionPatient populations eligible for monarchE and NATALEE trials differed. Nearly a third of the postmenopausal HRpos population, previously under upfront letrozole treatment, met the NATALEE prognostic eligibility criteria. As certain eligible groups had a prognosis similar to non-eligible patients, it might be interesting to explore additional patient groups for CDK4/6i therapy.

Pulmonary haemorrhage and haemoptysis associated with bevacizumab-related treatment regimens: a retrospective, pharmacovigilance study using the FAERS database.

Background: Bevacizumab (BV) is widely used in routine cancer treatment and clinical therapy in combination with many other agents. This study aims to describe and analyse post-market cases of pulmonary haemorrhage and haemoptysis reported with different BV treatment regimens by mining data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: Data were collected from the FAERS database between 2004 Q1 and 2023 Q1. Disproportionality analysis including the reporting odds ratio (ROR) was employed to quantify the signals of disproportionate reporting of pulmonary haemorrhage and haemoptysis adverse events (AEs) associated with BV-related treatment regimens. The demographic characteristics, time to onset and outcomes were further clarified. Results: A total of 55,184 BV-associated reports were extracted from the FAERS database, of which 497 reports related to pulmonary haemorrhage and haemoptysis. Overall, the median onset time of pulmonary haemorrhage and haemoptysis AEs was 43 days (interquartile range (IQR) 15-117 days). In the subgroup analysis, BV plus targeted therapy had the longest median onset time of 90.5 days (IQR 34-178.5 days), while BV plus chemotherapy had the shortest of 40.5 days (IQR 14-90.25). BV plus chemotherapy disproportionately reported the highest percentage of death (148 deaths out of 292 cases, 50.68%). Moreover, the BV-related treatments including four subgroups in our study demonstrated the positive signals with the association of disproportionate reporting of pulmonary haemorrhage and haemoptysis. Notably, BV plus chemotherapy showed a significant higher reporting risk in pulmonary haemorrhage and haemoptysis signals of disproportionate reporting in comparison to BV monotherapy (ROR 5.35 [95% CI, 4.78-6.02] vs. ROR 4.19 [95% CI, 3.56-4.91], p = 0.0147). Conclusion: This study characterized the reporting of pulmonary haemorrhage and haemoptysis, along with the time to onset and demographic characteristics among different BV-related treatment options. It could provide valuable evidence for further studies and clinical practice of BV.