Small molecule agents for triple negative breast cancer: Current status and future prospects.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor prognosis. The number of cases increased by 2.26 million in 2020, making it the most commonly diagnosed cancer type in the world. TNBCs lack hormone receptor (HR) and human epidermal growth factor 2 (HER2), which limits treatment options. Currently, paclitaxel-based drugs combined with other chemotherapeutics remain the main treatment for TNBC. There is currently no consensus on the best therapeutic regimen for TNBC. However, there have been successful clinical trials exploring large-molecule monoclonal antibodies, small-molecule targeted drugs, and novel antibody-drug conjugate (ADC). Although monoclonal antibodies have produced clinical success, their large molecular weight can limit therapeutic benefits. It is worth noting that in the past 30 years, the FDA has approved small molecule drugs for HER2-positive breast cancers. The lack of effective targets and the occurrence of drug resistance pose significant challenges in the treatment of TNBC. To improve the prognosis of TNBC, it is crucial to search for effective targets and to overcome drug resistance. This review examines the clinical efficacy, adverse effects, resistance mechanisms, and potential solutions of targeted small molecule drugs in both monotherapies and combination therapies. New therapeutic targets, including nuclear export protein 1 (XPO1) and hedgehog (Hh), are emerging as potential options for researchers and become integrated into clinical trials for TNBC. Additionally, there is growing interest in the potential of targeted protein degradation chimeras (PROTACs), degraders of rogue proteins, as a future therapy direction. This review provides potentially valuable insights with clinical implications.

Chinese herbal medicines for prostate cancer therapy: From experimental research to clinical practice.

Prostate cancer remains the second most common malignancy in men worldwide, is a global health issue, and poses a huge health burden. Precision medicine provides more treatment options for prostate cancer patients, but its popularity, drug resistance, and adverse reactions still need to be focused on. Chinese herbal medicines (CHMs) have been widely accepted as an alternative therapy for cancer, with the advantages of multiple targets, multiple pathways, and low toxicity. We searched the experimental research and clinical practice of CHMs for prostate cancer treatment published in PubMed, Embase, and Web of Science in the last five years. We found five CHM formulas and six single CHM extracts as well as 12 CHM-derived compounds, which showed induction of apoptosis, autophagy, and cell cycle arrest, suppression of angiogenesis, proliferation, and migration of prostate cancer cells, reversal of drug resistance, and enhancement of anti-tumor immunity. The mechanisms of action include the PI3K/Akt/mTOR, AR, EGFR and Wnt/ß-catenin signaling pathways, which are commonly implicated in the development of prostate cancer. We also summarized the advantages of CHMs in patients with hormone-sensitive and castration-resistant prostate cancer and provided ideas for their further experimental design and application.

Traditional Chinese medicines for non-small cell lung cancer: Therapies and mechanisms.

The most common subtype of lung cancer is non-small cell lung cancer (NSCLC), which has a poor prognosis and seriously threatens the health of human beings. The multidisciplinary comprehensive treatment model has gradually become the mainstream of NSCLC treatment. Traditional Chinese medicine (TCM) can be used effectively either as an adjunctive therapy or alone throughout the NSCLC therapy, which has a significant impact on survival, quality of life, and reduction of toxicity. Therefore, this paper reviewed the theoretical basis, the latest clinical application, and combined treatment mechanisms in order to explore the advantage stage of TCM treatment and the synergistic therapeutic mechanisms.

Comparison of efficacy and safety of bevacizumab biosimilar and original bevacizumab in non-squamous non-small cell lung cancer: a systematic review and meta-analysis.

Background: Bevacizumab (Avastin®), a monoclonal antibody targeting vascular endothelial growth factor (VEGF)-A, is widely used in treating a variety of malignant tumors. Several biosimilars of bevacizumab have been developed and marketed with the expiration of bevacizumab's patent. The objective of this study was to collate available data from head-to-head randomized controlled trials (RCTs) and evaluate the efficacy and safety of biosimilar bevacizumab compared with the bevacizumab (Avastin®) in patients with non-squamous non-small cell lung cancer (NSCLC). Methods: Literature search of Web of Science, PubMed, Cochrane Library, EMBASE, and ClinicalTrials.gov was performed from inception until October 15, 2021. The efficacy outcome indicators were objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). The occurrence of adverse events (AEs) was evaluated for safety outcome. Results: Ten RCTs recruiting 6,416 patients with non-squamous NSCLC were included. All RCTs studies included the biosimilar bevacizumab group as the experimental group and the original bevacizumab group as the control group. The patients in the experimental group and control group received the same dose and duration of chemotherapy combined with carboplatin and paclitaxel. The results of meta-analysis showed that there were no significant differences in ORR [risk ratio (RR): 0.97, 95% confidence interval (95% CI): 0.93-1.02. P=0.841, I2=0], PFS (RR: 1.04, 95% CI: 0.98-1.10, P=0.235, I2=0) and OS (RR: 1.05, 95% CI: 1.00-1.10, P=0.692, I2=0) between the biomarker and original groups. The P values of ORR, PFS and OS were 0.533, 0.970 and 0.916 respectively as shown by Egger's test, suggesting that there was no publication bias. Subgroup analysis showed no significant differences in ORR, PFS, and OS between the Chinese and multicenter trials. The pooled incidence rate of AEs between two groups was similar, and there was also no significant difference between the two groups. Discussion: This is the first study to independently report biosimilar bevacizumab in a meta-analysis on NSCLC treatment. The results showed that biosimilar bevacizumab had similar efficacy and safety compared with the original bevacizumab. Trial Registration: PROSPERO registration No. CRD42021276991.

Case Report: Afatinib Sensitivity in Rare EGFR E746_L747delinsIP Mutated LUAD With Peritoneal Metastases.

Patients with non-small cell lung cancer harboring the epidermal growth factor receptor (EGFR)-sensitive mutations are known to benefit significantly from EGFR tyrosine kinase inhibitors (TKIs), such as erlotinib, gefitinib, icotinib, or afatinib. However, the efficacy of EGFR-TKIs against rare mutations has not yet been well investigated. Here, we report a female patient with advanced lung adenocarcinoma (LUAD), carrying a rare mutation of EGFR Exon19 E746_L747delinsIP, who was administered first-generation EGFR-TKIs as the first-line treatment. The patient continued to progress slowly until peritoneal metastases have occurred. Subsequently, the patient was treated with anlotinib for 5 months until disease progression. Given the finding of the same EGFR rare mutation in peritoneal effusion without other EGFR-TKI resistance mutations, the patient received afatinib with a tremendous response. Our results may be of clinical relevance for patients with LUAD carrying this rare mutation, and these findings warrant further investigation.

Long Noncoding RNA: Shining Stars in the Immune Microenvironment of Gastric Cancer.

Gastric cancer (GC) is a kind of malignant tumor disease that poses a serious threat to human health. The GC immune microenvironment (TIME) is a very complex tumor microenvironment, mainly composed of infiltrating immune cells, extracellular matrix, tumor-associated fibroblasts, cytokines and chemokines, all of which play a key role in inhibiting or promoting tumor development and affecting tumor prognosis. Long non-coding RNA (lncRNA) is a non-coding RNA with a transcript length is more than 200 nucleotides. LncRNAs are expressed in various infiltrating immune cells in TIME and are involved in innate and adaptive immune regulation, which is closely related to immune escape, migration and invasion of tumor cells. LncRNA-targeted therapeutic effect prediction for GC immunotherapy provides a new approach for clinical research on the disease.

The Association between Leukocyte and Its Subtypes and Benign Breast Disease: The TCLSIH Cohort Study.

Inflammation plays a crucial role in the formation of benign breast disease. Given the limited study to explore the association between leukocyte as an indicator of immune system and benign breast disease, we used data from a large cross-sectional study to investigate association between leukocyte and its subtypes and benign breast disease among women in the general population. The data were derived from baseline data of the Tianjin chronic low-grade systemic inflammation and health (TCLSIH) cohort study during 2014 and 2016. Breast thickness and nodules status were assessed by using ultrasonography. Leukocyte and its subtype counts were carried out using the automated hematology analyzer. Multiple logistic regression analysis was used to examine the association between leukocyte and its subtypes and prevalence of benign breast disease. In the present study, the prevalence of benign breast disease was 20.9%. After adjustments for potentially confounding factors, the odds ratios (95% confidence interval) for benign breast disease across lymphocyte quintiles were as follows: 1.00 (reference), 0.99 (0.82, 1.2), 0.85 (0.69, 1.04), 0.84 (0.68, 1.02), and 0.75 (0.61, 0.92) (P for trend = 0.002). An inverse association between lymphocyte counts and benign breast disease was found, but leukocyte and other subtypes have nothing to do with benign breast disease. Further prospective studies are needed to determine the findings.

Anticancer effects of curcumin on nude mice bearing lung cancer A549 cell subsets SP and NSP cells.

Curcumin is a key polyphenolic curcuminoid extracted from the root of turmeric rhizome Curcuma longa Linn, which is a frequently used Chinese herb for the treatment of cancer. The aim of the present study was to investigate the mechanism of the inhibitory effects of curcumin on nude mice with lung cancer A549 cell subsets side population (SP) and non-SP (NSP) cells. BALB/c mice were subcutaneously injected with the tumor cells of A549 SP or NSP subsets consisting of 1×109 cells/l (0.2 ml in total). After 16 days of inoculation with A549, the mice were intraperitoneally injected with curcumin (100 mg/kg, 0.2 ml) once every other day, eight times in total. A series of assays were performed to detect the effects of curcumin on: i) Tumor weight and size; ii) Notch and hypoxia inducible factor 1 (HIF-1) mRNA expression by quantitative polymerase chain reaction; and iii) vascular endothelial growth factor (VEGF) and nuclear factor-κB (NF-κB) by immunohistochemistry. It was determined that curcumin decreased the tumor weight and size, downregulated the expression of Notch and HIF-1 mRNA and suppressed the VEGF and NF-κB expression. These results indicated that curcumin inhibited lung cancer growth through the regulation of angiogenesis mediated by VEGF signaling.

Genetic and epigenetic silencing of mircoRNA-506-3p enhances COTL1 oncogene expression to foster non-small lung cancer progression.

Although previous studies suggested that microRNA-506-3p (miR-506-3p) was frequently downregulated, and functioned as a tumor suppressor in several cancers, the biological role and intrinsic regulatory mechanisms of miR-506-3p in non-small cell lung cancer (NSCLC) remain elusive. The present study found miR-506-3p expression was downregulated in advanced NSCLC tissues and cell lines. The expression of miR-506-3p in NSCLC was inversely correlated with larger tumor size, advanced TNM stage and lymph node metastasis. In addition, we also found patients with lower expression of miR-506-3p had a poor prognosis than those patients with higher expression of miR-506-3p. Function studies demonstrated that aberrant miR-506-3p expression modulates tumor cell growth, cell mobility, cell migration and invasion in vitro and in vivo. Mechanistic investigations manifested that coactosin-like protein 1 (COTL1) was a direct downstream target of miR-506-3p. Knockdown of COTL1 mimicked the tumor-suppressive effects of miR-506-3p overexpression in A549 cells, whereas COTL1 overexpression enhanced the tumorigenic function in HCC827 cells. Importantly, we also found GATA3 transcriptionally actives miR-506-3p expression, and the long non-coding RNA urothelial carcinoma-associated 1 (UCA1) exerts oncogenic function in NSCLC by competitively 'sponging' miRNA-506. Together, our combined results elucidated genetic and epigenetic silencing of miR-506-3p enhances COTL1 oncogene expression to foster NSCLC progression.