Treatment Of Breast Cancer Research Articles

A feasible strategy for fabricating pH-responsive SN-38 loaded europium metal-organic framework delivery for promising treatment for breast cancer

One of the significant challenges in cancer therapy is the development of biocompatible drug delivery systems (DDS) with enhanced penetration retention effect (EPR) and precision targeting. The current study aimed to establish a one-pot synthesis of 7-ethyl-10-hydroxy camptothecin (SN-38) loaded europium-metal-organic framework (SN-38@Eu-MOF) and evaluate its anticancer potential against breast cancer. High drug loading efficiency (85.3 ± 0.02% in 48h at pH 5.0) and pH-sensitive regulated release of drug SN-38 were two characteristics of the fabricated Eu-MOFs. According to material characterization, the material's surface formed a monodispersed homogeneous rod-shaped structure adorned with SN-38, with an average particle size of 72 ± 0.23nm. Results of anticancer assays demonstrated that when compared to SN-38 alone, SN-38@Eu-MOFs showed improved anticancer potential in breast cancer cells (MCF-7 and MDA-MB-231). According to the mechanism of anticancer potential, SN-38@Eu-MOFs increased reactive oxygen species (ROS) levels and caused mitochondrial malfunction and DNA damage, which resulted in apoptosis. The study's findings indicate that SN-38@Eu-MOFs is a potentially biocompatible nanomaterial for drug delivery systems for treating breast cancer and other pharmaceutical applications.

Evaluation of the Protective Effects of Vitamins E and D on Oxidative Stress and Inflammation Caused by Tamoxifen in the Renal Tissue of Female Wistar Rats

Background: Tamoxifen is an effective drug for breast cancer treatment and its side effects are the production of reactive oxygen species and kidney damage. As antioxidants, vitamins E and D may help decrease kidney dysfunction. Objectives: In the present study, the protective effects of vitamins E and D on renal toxicity caused by tamoxifen in female Wistar rats were investigated. Materials and Methods: Twenty-five adult female rats weighing 180-200 were randomly divided into five groups with 5 rats. Group C, T, TE, TD, and TED were treated with olive oil, tamoxifen, tamoxifen + vitamin E, tamoxifen +vitamin D, and tamoxifen + both vitamins for four weeks. ELISA Kits measured the oxidant and antioxidant tests and TNF-α in kidney tissue. The spectrophotometric method measured urea, uric acid, and creatinine in serum and urine. Results: Tamoxifen significantly decreased the weight of rats, GPx, CAT, SOD levels and increased TNF-α, urinary creatinine level and, serum uric acid, urea levels (P < 0.05). But, treatment with vitamin D and simultaneous administration of vitamins led to a significant decrease in the level of (TNF-α) compared to the tamoxifen group (p < 0.01). Also, the histopathology results showed that the simultaneous administration of vitamins has significantly resolved the damage caused by the use of tamoxifen. Conclusion: The present study's findings showed that using vitamins E and D prevents kidney damage through antioxidant and anti-inflammatory effects. In addition, using vitamins E and D probably showed stronger synergistic effects against kidney damage.

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.

V. Craig Jordan obituary: pharmacologist who revolutionized breast cancer treatments.

V. Craig Jordan obituary: pharmacologist who revolutionized breast cancer treatments.

The Chiraiya project: a retrospective analysis of breast cancer detection gaps addressed via mobile mammography in Jammu Province, India

BackgroundBreast cancer remains a pervasive threat to women worldwide, with increasing incidence rates necessitating effective screening strategies. Timely detection with mammography has emerged as the primary tool for mass screening. This retrospective study, which is part of the Chiraiya Project, aimed to evaluate breast lesion patients identified during opportunistic mammography screening camps in Jammu Province, India.MethodsA total of 1505 women aged 40 years and older were screened using a mobile mammographic unit over a five-year period, excluding 2020 and 2021 due to the COVID-19 pandemic. The inclusion criterion was women in the specified age group, while the exclusion criterion was women with open breast wounds, history of breast cancer or a history of breast surgery. The screening process involved comprehensive data collection using a detailed Proforma, followed by mammographic assessments conducted within strategically stationed mobile units. Radiological interpretations utilizing the BI-RADS system were performed, accompanied by meticulous documentation of patient demographics, habits, literacy, medical history, and breastfeeding practices. Participants were recruited through collaborations with NGOs, army camps, village panchayats, and urban cooperatives. Screening camps were scheduled periodically, with each camp accommodating 90 patients or fewer.ResultsAmong the 1505 patients, most were aged 45–50 years. The number of screenings increased yearly, peaking at 441 in 2022. The BI-RADS II was the most common finding (48.77%), indicating the presence of benign lesions, while the BI-RADS 0 (32.96%) required further evaluation. Higher-risk categories (BI-RADS III, IV, V) were less common, with BI-RADS V being the rarest. Follow-up adherence was highest in the BI-RADS III, IV, and V categories, with BI-RADS V achieving 100% follow-up. However, only 320 of 496 BI-RADS 0 patients were followed up, indicating a gap in continuity of care. The overall follow-up rate was 66.89%. Compared to urban areas, rural areas demonstrated greater screening uptake but lower follow-up rates, highlighting the need for tailored interventions to improve follow-up care access, especially in rural contexts.ConclusionThis study underscores the efficacy of a mobile mammographic unit in reaching marginalized populations. Adherence to screening protocols has emerged as a linchpin for early detection, improved prognosis, and holistic public health enhancement. Addressing misconceptions surrounding mammographic screenings, especially in rural settings, is crucial. These findings call for intensified efforts in advocacy and education to promote the benefits of breast cancer screening initiatives. Future interventions should prioritize improving access to follow-up care and addressing screening to enhance breast cancer management in Jammu Province.

Physiological mechanisms of exercise related to prevention and treatment of breast cancer: A review

Background: Considering limitations related to intensity, duration, and mode of exercise and possible physiological mechanisms, this study aimed to summarize the physiological mechanisms emphasizing inflammation, angiogenesis, and immunology of different exercises related to prevention and treatment of breast cancer. Methods: In the current review study, different platforms were analyzed including PubMed, Scopus, Cochrane, Embase, Web of Science, Science Direct, Google Scholar, and Research Gate as well as Iranian databases such as Scientific Information Database (SID) and Magiran. The data was reviewed until May 2024. Search keywords included “exercise", "sport”, “physical exercise”, “intensity, training”, “breast cancer”, “inflammation”, “angiogenesis”,” immunology”, and “physiological mechanisms”. Results: Among several proposed mechanisms, inflammation, immunity and angiogenesis have been mentioned as important indices but there are ambiguities regarding the influence of different intensities and durations of exercise on breast cancer prevention and treatment. Other effective factors such as the effect of exercise on gene regulation and some other mechanisms have been proposed as possible mediators. Conclusion: According to some previous studies, aerobic exercise induces positive effects on preventing and treating breast cancer through reducing inflammation, improving angiogenesis, and enhancing immunological mechanisms. Regarding duration and intensity, long term regular exercise (>8 weeks), in the form of aerobic and especially high intensity interval training (HIIT) reduces inflammation. while the effect of short-term exercise training is not clear yet and high intensity exercise may induce suppressing effects on the immune system. Therefore, the effect of intensity and duration of exercise on physiological mechanisms must be clarified.

Significance of zoledronic acid in the adjuvant therapy in patients with breast cancer

Introduction. Zoledronic acid is a medicine belonging to the bisphosphonate group. Its action is to inhibit the function of osteoclasts, which leads to a reduction in bone resorption. This preparation has a proven effect in the treatment of osteoporosis and Paget’s disease. Bisphosphonates have also found use in the treatment of breast cancer. Studies conducted for many years indicate that zoledronic acid works most favorably in combination with adjuvant therapy. Breast cancer patients who are postmenopausal and being treated with chemotherapy are at risk of bone mass loss and hypercalcemia. Bisphosphonates effectively manage this. In addition, zoledronic acid indirectly exerts anticancer effects by modulating the immune system. All this allows us to conclude that taking this drug reduces the risk of bone metastasis in breast cancer patients. Dosage is also key in all this. There are several regimens offered to osteoporosis and breast cancer patients. So far, the following have been studied: conventional dosing (4 mg IV every 3-4 weeks), maintenance dosing (4 mg IV every 3-6 months) and metronomic dosing (1 mg IV weekly). It cannot be ruled out that each of these regimens may have a different antitumor effect. By reviewing scientific works, we aim to present the treatment options with zoledronic acid for breast cancer patients. We will describe the impact on their results depending on the dosage and we will present the other side of the coin, which are the side effects of taking this preparation. Aim. This review provides an overview of the effects and impact of zoledronic acid in adjuvant therapy in patients with breast cancer. Material and methods. The article presents the current state of knowledge on zoledronic acid as an adjuvant treatment option in breast cancer patients. It is a detailed literature review using Google Scholar, PubMed and Journal of Education Health and Sport platforms. Publications using the following key words were analyzed: bisphosphonates, zoledronic acid, osteoporosis, breast cancer, bone metastases. Conclusion. Women diagnosed with breast cancer should be treated in a multidisciplinary manner. We treat early detected cancers to achieve complete remission. Long-term survival is our primary goal, and in pursuing it we should consider the potential impact of this treatment on the patient’s skeletal system. Clinical studies allow us to conclude that there is a correlation between the initiation of antiresorptive therapy at an early stage of cancer and overall survival. Additionally, zoledronic acid significantly reduced the number of fractures. The collected data allow us to conclude that the addition of zoledronic acid to the established treatment regimens has a potentially positive effect on the group of postmenopausal patients undergoing tamoxifen treatment or with existing bone metastases. Keywords: bisphosphonates, zoledronic acid, breast cancer, osteoporosis, bone metastases.

Nano-enabled thermo-responsive local delivery of tamoxifen and carvacrol for enhanced anticancer action

Tamoxifen (TMX) is widely employed in the treatment of breast cancer. However, owing to its poor solubility (BCS class II drug), rapid first-pass metabolism and free radical generation leading to hepatotoxicity, a better drug delivery platform is required. A sufficient concentration of TMX must be achieved while avoiding harm to healthy cells in the target for effective therapy. Carvacrol (CV), a natural monoterpene, has reported antitumor activity and cell growth inhibition effects on MCF-7 and MDA-MB-231 breast cancer cells. In the current study, TMX and CVR-loaded nano-emulsion was prepared and incorporated into thermosensitive poloxamer gel to achieve enhanced anticancer action locally. Box-Behnken Design was employed to extensively optimize the prepared formulation wherein the droplet size obtained was 97.53 ± 1.80 nm and PDI was 0.195 ± 0.0026. The developed thermogel was characterized for gelation temperature, rheology, hemolysis and drug release. The gelation and higher viscosity were attended closer to body temperature (37 ± 0.5 °C), and showed retarded drug release (∼60 % after 5 days). The developed thermogel showed 16.02 % hemolysis as compared to 71.89 % from free TMX. Further, In-vitro cell culture studies of the developed formulation revealed significantly enhanced cytotoxicity and almost 6-fold higher cellular internalization. In addition, dose-dependent lowering of mitochondrial membrane potential and 5.9-fold higher ROS production by TMX-CVR-NE was observed. Therefore, an in-situ thermo-gel depot of TMX and CVR imparted an attractive way for the controlled delivery and enhanced local activity of TMX in breast cancer.

Stimuli-responsive drug delivery system for breast cancer treatment

In the annals of cancer treatment within the domain of nanomedicine, the utilization of stimulus-response drug delivery systems has emerged as a focal point of considerable significance. While a multitude of diverse methodologies are presently employed for the treatment of tumors, the preeminent and most efficacious approach, particularly in the context of intricate scenarios, pertains to the targeted administration of therapeutic and diagnostic nanoparticles into the tumor milieu. These nanoparticles exhibit the inherent potential to acclimatize to the nuanced microenvironment of the tumor, thereby surmounting the challenges posed by tumor heterogeneity. The stimuli-responsive attributes inherent to nanoscale particles can broadly be delineated into two distinct categories: endogenous and exogenous, with a minority manifesting characteristics of both classifications. This scientific review provides an overview of the discourse surrounding exogenous drug delivery systems, which leverage ultrasound and magnetic fields as responsive stimuli, alongside endogenous drug delivery systems employing pH variations and enzymatic cues as triggering mechanisms. The findings of this review emphasize the significance of stimuli-responsive drug delivery systems as a promising strategy to enhance the specificity and efficacy within the sphere of breast cancer treatment. Finally, the review concludes with a discussion on the future directions and potential clinical applications of these systems.

Retraction Note: EGFR Targeted Paclitaxel and Piperine Co-loaded Liposomes for the Treatment of Triple Negative Breast Cancer.

Retraction Note: EGFR Targeted Paclitaxel and Piperine Co-loaded Liposomes for the Treatment of Triple Negative Breast Cancer.

Immune and Gene-expression Profiling in Estrogen Receptor Low and Negative Early Breast Cancer.

The cut-off of < 1% positive cells to define estrogen receptor (ER) negativity by immunohistochemistry (IHC) in breast cancer (BC) is debated. We explored the tumor immune microenvironment and gene-expression profile of patients with early-stage HER2-negative ER-low (ER 1-9%) BC, comparing them to ER-negative (ER < 1%) and ER-intermediate (ER 10-50%) tumors. Among 921 patients with early-stage I-III, ER ≤ 50%, HER2-negative BCs, tumors were classified as ER-negative (n = 712), ER-low (n = 128), or ER-intermediate (n = 81). Tumor-infiltrating lymphocytes (TILs) were evaluated. CD8+, FOXP3+ cells, and PD-L1 status were assessed by IHC and quantified by digital pathology. We analyzed 776 BC-related genes in 116 samples. All tests were 2-sided at < 0.05 significance level. ER-low and ER-negative tumors exhibited similar median TILs, significantly higher than ER-intermediate tumors. CD8/FOXP3 ratio and PD-L1 positivity rates were comparable between ER-low and ER-negative groups. These groups showed similar enrichment in Basal-like intrinsic subtypes and comparable expression of immune-related genes. ER-low and ER-intermediate tumors showed significant transcriptomic differences. High TILs (≥30%) were associated with improved relapse-free survival (RFS) in ER-low (5-year RFS 78.6% vs 66.2%, log-rank p = .033, hazard ratio (HR) 0.37 [95% CI 0.15-0.96]) and ER-negative patients (5-year RFS 85.2% vs 69.8%, log-rank p < .001, HR 0.41 [95% CI 0.27-0.60]). ER-low and ER-negative tumors are similar biological and molecular entities, supporting their comparable clinical outcomes and treatment responses, including to immunotherapy. Our findings contribute to the growing evidence calling for a reevaluation of ER-positive BC classification and management, aligning ER-low and ER-negative tumors more closely.

Relationship between Screening, Diagnostic Mammograms, Hospital Admissions, and Mortality Rates from Breast Cancer

Background: Breast cancer is the most common type of cancer worldwide. If diagnosed and treated early, it has a high chance of cure, and for this, screening tests are necessary, namely mammograms, which are the most commonly used. The objective of this study was to analyze the association between the number of screening and diagnostic mammograms and the number of hospitalizations and deaths from breast cancer. Methods: This is a cross-sectional, analytical, retrospective study with secondary data made available by the Ministry of Health. Pearson correlation analysis was employed to assess whether the number of mammograms is associated with the number of deaths and hospitalizations, Poisson regression was used to assess whether an increase in the number of mammograms and hospitalizations is related to the number of deaths, and the Cox–Stuart test was used to analyze the temporal trend of the variables under study and the projection of time series. Results: There was a strong positive correlation for all age groups when relating the variables hospitalizations and deaths, a moderate-to-strong correlation for the variables mammography and hospitalization, and a weak correlation for the variables mammography and death. There was no statistical significance in the relationship between the number of mammograms and deaths, whereas the hospitalization variable had a significant impact in relation to death, increasing the chance by 0.015%. There has also been a significant growth trend in the variables deaths and hospitalizations in Brazil over the years. Conclusions: A growing trend was identified from 2013 to 2021, both in hospitalizations and deaths, thus suggesting that strategies aimed at reformulating public health policies are necessary for earlier diagnosis in order to improve the treatment of breast cancer and the prognosis of the disease.

Postlumpectomy Mammography for Management of Breast Cancers With Microcalcifications

This cohort study examines use of lumpectomy margin status in managing microcalcifications in breast cancer.

In silico study suggests potential drugs that target CD151 to treat breast cancer and lioblastoma.

Recently tetraspanin CD151 has been identified as an important biological target involved in metastatic processes which include cell adhesion, tumor progression processes, and so forth in different types of cancers, such as breast cancer and glioblastoma. This in Silico study considered 1603 compounds from the Food and Drug Administration database, after performing an ADMET analysis; we selected 853 ligands, which were used for docking analysis. The most promising ligands were selected from docking studies, based on two criteria: (a) showed lowest affinity to the CD151 protein and (b) they interact with the QRD motif, located in the second extracellular loop. Furthermore, we investigate the stability of the protein-ligand complexes through MD simulations as well as free energy MM-PBSA calculations. From these results, loperamide and glipizide were identified as the best evaluated drugs. We suggest an in vitro analysis is needed to confirm our in silico prediction studies.

A survey of women diagnosed with breast cancer experiencing oncology treatment-induced hot flushes: identification of specific characteristics as predictors of hot flush occurrence, frequency, and severity.

More women diagnosed with breast cancer (BC) are living with oncology treatment-induced hot flushes (HFs). This Australian-based survey explores why some women experience more severe or ongoing HF and whether specific population characteristics are predictive of HF occurrence, frequency, and/or severity. A non-probabilistic anonymous survey distributed online (Register4) and two Australian hospitals collected demographic and clinical information. Eligibility was consenting Australian-based women, 18 years and over, with a primary BC diagnosis. Analysis included linear and logistic regression models. A total of 324 survey responses were analyzed. Chemotherapy and hormone therapy were each associated with HF occurrence (aOR = 2.92, 95% CI [1.27, 6.70], p = 0.01; and aOR = 7.50, 95% CI [3.02, 18.62], p < 0.001) and in combination (aOR = 5.98, 95% CI [2.61, 13.69], p < 0.001). Increased self-reported anxiety at BC diagnosis was significantly associated with HF frequency and severity scores (aCO = 0.71, 95% CI [0.31, 1.12], p = 0.001; and aCO = 0.44, 95% CI [0.33, 0.55], p < 0.001). Postmenopausal women had significantly lower HF severity and frequency scores than premenopausal women (aCO = -0.93, 95% CI [-1.62, -0.25], p = 0.008; and aCO = -2.62, 95% CI [-5.14, -0.11], p = 0.041). Women with BC receiving chemotherapy and/or hormone therapy and premenopausal or experiencing elevated anxiety and/or stress will likely experience more severe oncology treatment-related HFs. HFs continue across the BC treatment trajectory with women >5-year survivorship still reporting life impacts, with premenopausal women at the time ofBCdiagnosis at higher risk of experiencing severe and more frequentoncology treatment-induced HFs than postmenopausal women. Women at high risk require information on methods to moderate HF potential life impacts and maintain treatment compliance.

Evaluating the accuracy of large language model (ChatGPT) in providing information on metastatic breast cancer

Background: Artificial intelligence (AI), particularly large language models like ChatGPT developed by OpenAI, has shown promise in transforming various domains, including medicine. ChatGPT's ability to generate human-like responses to a wide array of subjects has been leveraged in various fields, notably passing the rigorous United States Medical Licensing Examination (USMLE) Step 1. However, its proficiency in responding to inquiries related to breast cancer, a prevalent and complex disease spectrum, remains underexplored. Objective: This study aims to evaluate the accuracy and comprehensiveness of ChatGPT's responses to commonly asked questions about breast cancer, filling a critical gap in the literature and understanding its potential in enhancing patient education and support within the realm of breast cancer management. Methods: A list of 100 questions was curated from frequently asked questions on Cancer.net and the National Breast Cancer Foundation's website, combined with inquiries commonly received in clinical practice. These questions were entered into the ChatGPT (Version 4.0) user interface, and the responses were evaluated by two primary experts for accuracy, using a four-point scale. Discrepancies in scoring were resolved by additional expert reviews. Results: Out of the 100 evaluated responses, 5 were entirely inaccurate, 22 partially accurate, 42 accurate but not comprehensive, and 31 highly accurate. The majority of responses across different categories were found to be at least accurate to a certain extent, demonstrating ChatGPT's potential in providing reliable information on breast cancer. Conclusions: ChatGPT exhibits potential as a supplementary resource for patient education on breast cancer. While its responses were generally accurate, the presence of inaccuracies highlights the importance of professional oversight.

Preparation of cardamonin and IR780 Co-loaded on Lycium barbarum polysaccharide nanoparticles and anti-tumor efficacy evaluation

To improve the therapeutic efficacy of cardamonin (CRD) in the treatment of breast cancer, Lycium barbarum polysaccharide (LBP) was selected as a nanocarrier for CRD and IR780 to prepare CRD-IR780@LBP nanoparticles (NPs) via antisolvent precipitation. CRD-IR780@LBP NPs demonstrated superior characteristics, such as sustainable drug release, high photothermal conversion, and good antitumor efficacy and secretion levels of cytokines (TNF-α, IL-6 and IL-2). The IC50 value of CRD-IR780@LBP NPs was 2.31 μg/mL, which was significantly lower than that of the pure CRD group (P < 0.0001). The tumor inhibition rate of CRD-IR780@LBP NPs was 80.03 %, which was a 1.58-fold increase compared to that of PTX injection. Furthermore, the ELISA results suggested that LBP can exert therapeutic effects by upregulating the expression levels of TNF-α, IL-6 and IL-2 (P < 0.01) without causing any apparent adverse effects on major tissues and organs. In conclusion, the CRD-IR780@LBP NPs prepared in this study can enhance the therapeutic efficacy of CRD against breast cancer via multiple synergistic anti-tumor mechanisms.

Homologous recombination deficiency status predicts response to immunotherapy-based treatment in non-small cell lung cancer patients.

Homologous recombination deficiency (HRD) is a biomarker that predicts response to ovarian cancer treatment with poly (ADP-ribose) polymerase (PARP) inhibitors or breast cancer treatment with first-line platinum-based chemotherapy. However, there are few studies on the prognosis of lung cancer patients treated with immune checkpoint inhibitor (ICI) therapy using HRD as a biomarker. We studied the relationship between HRD status and the effectiveness of first-line ICI-based therapy in EGFR/ALK wild-type metastatic non-small cell lung cancer patients (NSCLC) patients. This study included 22 treatment naïve NSCLC patients. The HRD score ranged from -26.37 to 92.34, with an average of 24.57. Based on analysis of the progression-free survival (PFS) data from the included NSCLC patients, threshold traversal was carried out. HRD (+) was defined as an HRD score of 31 or higher. Kaplan-Meier PFS survival analysis showed prolonged median PFS (mPFS) in NSCLC patients with HRD (+) versus HRD (-) (N/A vs. 7.0 ms, log-rank p = 0.029; HR 0.20, 95% CI: 0.04-0.96, likelihood-ratio p = 0.03). In patients with PD-L1 TPS ≥50% and HRD score ≥31 (co-status high), the mPFS was temporarily not reached during the follow-up period. In patients with PD-L1 TPS <1% and HRD score <31, the mPFS was 3 ms. Cox regression analysis showed that the hazard ratio of the co-status was 0.14 (95% CI: 0.04-0.54), which was a good prognostic factor, and the prognostic effect of co-status was better than that of HRD score alone. The HRD status can be identified as an independent significance in NSCLC patients treated with first-line ICI-based therapy.

Evaluation of the Mammalian Aquaporin Inhibitors Auphen and Z433927330 in Treating Breast Cancer

AQPs contribute to breast cancer progression and metastasis. We previously found that genetic inhibition of Aqp7 reduces primary tumor burden and metastasis in breast cancer. In this study, we utilized two AQP inhibitors, Auphen and Z433927330, to evaluate the efficacy of therapeutic inhibition of AQPs in breast cancer treatment. The inhibitors were evaluated in breast cancer for both cytotoxicity and metabolic stability assays across both murine and human breast cancer cell lines. Both AQP inhibitors also affected the expression of other AQP transcripts and proteins, which demonstrates compensatory regulation between AQP family members. As a single agent, Auphen treatment in vivo extended overall survival but did not impact primary or metastatic tumor burden. However, Auphen treatment made cells more responsive to chemotherapy (doxorubicin) or endocrine treatment (tamoxifen, fulvestrant). In fact, treatment with Tamoxifen reduced overall AQP7 protein expression. RNA-seq of breast cancer cells treated with Auphen identified mitochondrial metabolism genes as impacted by Auphen and may contribute to reducing mammary tumor progression, lung metastasis, and increased therapeutic efficacy of endocrine therapy in breast cancer. Interestingly, we found that Auphen and tamoxifen cooperate to reduce breast cancer cell viability, which suggests that Auphen treatment makes the cells more susceptible to Tamoxifen. Together, this study highlights AQPs as therapeutic vulnerabilities of breast cancer metastasis that are promising and should be exploited. However, the pharmacologic results suggest additional chemical refinements and optimization of AQP inhibition are needed to make these AQP inhibitors appropriate to use for therapeutic benefit in overcoming endocrine therapy resistance.

Enhanced expression of galectin-9 in triple negative breast cancer cells following radiotherapy: Implications for targeted therapy.

Optimizations are expected in the development of immunotherapy for the treatment of Triple-negative breast cancer (TNBC). We studied the expression of galectin-9 (Gal-9) after irradiation and assessed the differential impacts of its targeting with or without radiotherapy. Tumor resections from TNBC patients who received neoadjuvant radiotherapy revealed higher levels of Gal-9 in comparison to their baseline level, only in non-responder patients. Gal-9 expression was also found to be increased in TNBC tumor biopsies and cell lines after irradiation. We investigated the therapeutic advantage of targeting Gal-9 after radiotherapy in mice. Irradiated 4T1 cells or control non-irradiated 4T1 cells were injected into BALB/c mice. Anti-Gal-9 antibody treatment decreased tumor progression only in mice injected with irradiated 4T1 cells. This proof-of-concept study demonstrates that Gal-9 could be considered as a dynamic biomarker after radiotherapy for TNBC and suggests that Gal-9 induced-overexpression could represent an opportunity to develop new therapeutic strategies for TNBC patients.