Efficacy and safety of anlotinib as maintenance therapy after induction chemotherapy in extensive-stage small-cell lung cancer.

Anlotinib has been approved as the third-line or beyond treatment regimen for patients with extensive-stage small-cell lung cancer (ES-SCLC). However, it is indistinct whether there are survival benefits of anlotinib in the maintenance therapy of ES-SCLC. Therefore, this study aims to evaluate the efficacy and safety of anlotinib monotherapy as maintenance therapy after induction chemotherapy for patients with ES-SCLC. The median progression-free survival (mPFS) was considered to be the pivotal symbol as the primary endpoint. The median overall survival (mOS) and safety were recognized as the second endpoints. Eligible patients in stable status after first-line chemotherapy would subsequently accept oral anlotinib (12 mg/d, d1-d14, every 21 days as a course). The maintenance method was continued until disease progression or unmanageable toxicity occurred. The mPFS was 7.7 months (95% CI, 7.20-8.20 months) and the mOS was 11.0 months (95% CI, 9.19-12.82 months), respectively. The most common treatment-related adverse events were hypertension ( n = 9; 64.3%), fatigue ( n = 6; 42.9%), followed by decreased appetite ( n = 5; 35.7%), nausea ( n = 5; 35.7%), weight decrease ( n = 4; 28.6%), and rash ( n = 4; 28.6%). There were no patients who required dose reduction because of severe adverse events. Anlotinib achieved prospective efficacy and manageable safety in the maintenance treatment of ES-SCLC. These above outcomes demonstrated that anlotinib was a tolerable and potent maintenance treatment option after induction chemotherapy in ES-SCLC.

Immune checkpoint inhibitors for RET fusion non-small cell lung cancer: hopes and challenges.

Immune ch eckpoint inhibitors (ICIs) represent a milestone in advanced nonsmall cell lung cancer (NSCLC). Nevertheless, NSCLC with known oncogenic drivers has been overlooked in most studies evaluating anti-programmed death-1/programmed death ligand 1. Rearranged during transfection proto-oncogene (RET) gene fusion was identified in 1-2% of NSCLC patients. More recently, two selective RET inhibitors, selpercatinib and pralsetinib, demonstrated higher efficacy and good tolerability. In contrast, the activity of ICIs in RET fusion NSCLC has not been well characterized. Here, we analyzed the clinical data of ICIs and discussed the suitable time to introduce ICIs in RET fusion NSCLC. Finally, we put forward future strategies to adequately maximize the efficacy of ICIs treatment in patients with RET fusion NSCLC in the upcoming era of combination immunotherapies.

Hopes and failures in front-line advanced HER2-positive gastric cancer therapy.

Human epidermal growth-factor receptor 2 (HER2) was an important therapeutic target in gastric cancer. Through the last decade, strategy with trastuzumab-based chemotherapy remains the first-line standard of treatment in advanced HER2-positive gastric cancer. Based on the Trastuzumab for Gastric Cancer trial, trastuzumab plus systemic chemotherapy of cisplatin and fluoropyrimidine as the backbone was established as the first-line therapy in advanced HER2-positive gastric cancer. Since then, studies have explored the optimization of the front-line strategy, including the dose of trastuzumab, chemotherapy regimen and maintenance therapy. A large number of clinical trials were conducted to explore the optimal front-line therapy regimens, such as lapatinib and pertuzumab. Safe and effective first-line regimens are still lacking. Recently, two phase II studies of combining immune checkpoint inhibitor in first-line treatment of advanced HER2-positive gastric cancer showed promising results. The progress of immunotherapy has gradually promoted the development of front-line treatment of advanced HER2-positive gastric cancer to potential chemotherapy-free strategies. Therefore, this article reviewed these significant clinical trials and focus on the front-line treatment strategies for HER2-positive gastric cancer.

GPRC5A overexpression predicted advanced biological behaviors and poor prognosis in patients with gastric cancer.

G protein-coupled receptor, family C, group 5, member A (GPRC5A) had received attentions for its role in carcinogenesis and prognostic values in several types of cancer. However, the functional roles of GPRC5A in gastric cancer (GC) had never been elucidated. The expression levels of GPRC5A were detected by real-time quantitative reverse transcription PCR and Western blot in GC tissues and adjacent non-tumor tissues. GPRC5A expression in tissue sections of 106 GC samples was evaluated using immunohistochemistry. The staining results were compared with clinicopathological factors and to the prognosis of GC patients. The mRNA and protein expression levels of GPRC5A in gastric cancer tissues were higher than those in adjacent non-tumor tissues. Positive GPRC5A expression was significantly correlated with larger size of primary tumor, diffuse type (Lauren's classification), deeper serosal invasion, and more lymph node metastasis. In addition, Kaplan-Meier curve analysis demonstrated that GC patients with positive GPRC5A expression had poor prognosis than those with negative GPRC5A expression. GPRC5A expression was identified as an independent factor of the overall survival in GC patients by multivariate Cox analysis. Further, the overall survival difference existed between patients with GPRC5A positive and negative groups in GC patients with lymph node metastasis. Our results suggested that elevated levels of GPRC5A played significant roles in GC progression. GPRC5A could serve as a prognostic biomarker of GC.

Metformin use improves the survival of diabetic combined small-cell lung cancer patients.

Metformin has been reported having potential anticancer effect on kinds of solid tumors, but its role in combined small-cell lung cancer (C-SCLC) remains indistinct. This study aimed to explore whether metformin use has a prognosis benefit in diabetic C-SCLC patients. A total of 259 C-SCLC patients with diabetes were enrolled in our study. The clinicopathological parameters and survival data were collected and analyzed. The correlation between metformin use and clinicopathological characters was analyzed. Univariate and multivariate analyses were performed to investigate the prognostic significance of metformin use for C-SCLC. The metformin was used in 120 (46.3 %) patients. Our data showed that the metformin use decreased C-SCLC recurrence rate (p = 0.001). The median overall survival (OS) and disease-free survival (DFS) were significantly better in the metformin use group compared to non-metformin group (OS 19.0 vs 11.5 months, p < 0.001; DFS 10.5 vs 7.0 months, p < 0.001). Multivariate analyses indicated that metformin use was an independent prognostic factor for OS and DFS (p = 0.001 vs p = 0.018). The metformin use improved the long-term outcome of C-SCLC patients with diabetes, which might be considered a potential useful prognostic indicator and anticancer drug.

The regulatory role of activating transcription factor 2 in inflammation.

Activating transcription factor 2 (ATF2) is a member of the leucine zipper family of DNA-binding proteins and is widely distributed in tissues including the liver, lung, spleen, and kidney. Like c-Jun and c-Fos, ATF2 responds to stress-related stimuli and may thereby influence cell proliferation, inflammation, apoptosis, oncogenesis, neurological development and function, and skeletal remodeling. Recent studies clarify the regulatory role of ATF2 in inflammation and describe potential inhibitors of this protein. In this paper, we summarize the properties and functions of ATF2 and explore potential applications of ATF2 inhibitors as tools for research and for the development of immunosuppressive and anti-inflammatory drugs.

Therapeutic role of EGFR - Tyrosine kinase inhibitors in non-small cell lung cancer with leptomeningeal metastasis.

Leptomeningeal metastasis (LM) is a significant complication that advances fast and has a poor prognosis for patients with advanced non-small cell lung cancer (NSCLC) who have epidermal growth factor receptor (EGFR) mutations. Current therapies for LM are inconsistent and ineffective, and established techniques such as radiation, chemotherapy, and surgery continue to fall short of potential outcomes. Nonetheless, EGFR tyrosine kinase inhibitors (TKIs) exhibit potent anti-tumor activity and hold considerable promise for NSCLC patients with EGFR mutations. Thus, assessing EGFR-TKIs effectiveness in treating these central nervous system (CNS) problems is crucial. This review integrates current literature on the intracranial efficacy of EGFR-TKIs to explore the varying impacts of approved EGFR-TKIs in LM patients and the therapeutic possibilities presented by other EGFR-TKIs in development. To delineate the optimal clinical treatment strategy, further exploration is needed regarding the optimal sequencing of EGFR-TKIs and the selection of alternative therapy options following initial treatment failure with EGFR-TKIs.

Immunosenescence and immunotherapy in older NSCLC patients.

Nonsmall cell lung cancer (NSCLC) predominantly affects the elderly since its incidence and mortality rates skyrocket beyond the age of 65. The landscape of NSCLC treatment has been revolutionized by immune checkpoint inhibitors (ICIs), which have emerged after a long and mostly inactive period of conventional treatment protocols. However, there is limited data on the exact effects of these chemicals on older patients, whose care can be complicated by a variety of conditions. This highlights the need to understand the efficacy of emerging cancer medicines in older patients. In this study, we will review the data of ICIs from clinical trials that were relevant to older people with NSCLC and poor performance status. We will also discuss the role of immunosenescence in immunotherapy and biomarkers in predicting the efficacy of ICIs in patients with advanced NSCLC.

Identification and analysis of prognostic immune cell homeostasis characteristics in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is one of the most invasive malignant tumor of the respiratory system. It is also the common pathological type leading to the death of LUAD. Maintaining the homeostasis of immune cells is an important way for anti-tumor immunotherapy. However, the biological significance of maintaining immune homeostasis and immune therapeutic effect has not been well studied. METHODS: We constructed a diagnostic and prognostic model for LUAD based on B and T cells homeostasis-related genes. Minimum absolute contraction and selection operator (LASSO) analysis and multivariate Cox regression are used to identify the prognostic gene signatures. Based on the overall survival time and survival status of LUAD patients, a 10-gene prognostic model composed of ABL1, BAK1, IKBKB, PPP2R3C, CCNB2, CORO1A, FADD, P2RX7, TNFSF14, and ZC3H8 was subsequently identified as prognostic markers from The Cancer Genome Atlas (TCGA)-LUAD to develop a prognostic signature. This study constructed a gene prognosis model based on gene expression profiles and corresponding survival information through survival analysis, as well as 1-year, 3-year, and 5-year ROC curve analysis. Enrichment analysis attempted to reveal the potential mechanism of action and molecular pathway of prognostic genes. The CIBERSORT algorithm calculated the infiltration degree of 22 immune cells in each sample and compared the difference of immune cell infiltration between high-risk group and low-risk group. At the cellular level, PCR and CKK8 experiments were used to verify the differences in the expression of the constructed 10-gene model and its effects on cell viability, respectively. The experimental results supported the significant biological significance and potential application value of the molecular model in the prognosis of lung cancer. Enrichment analyses showed that these genes were mainly related to lymphocyte homeostasis. CONCLUSION: We identified a novel immune cell homeostasis prognostic signature. Targeting these immune cell homeostasis prognostic genes may be an alternative for LUAD treatment. The reliability of the prediction model was confirmed at bioinformatics level, cellular level, and gene level.

Treatment Advances in Lung Cancer with Leptomeningeal Metastasis.

Leptomeningeal metastasis (LM) is a serious and often fatal complication in patients with advanced lung cancer, resulting in significant neurological deficits, decreased quality of life, and a poor prognosis. This article summarizes current research advances in treating lung cancer with meningeal metastases, discusses clinical challenges, and explores treatment strategies. Through an extensive review of relevant clinical trial reports and screening of recent conference abstracts, we collected clinical data on treating patients with lung cancer with meningeal metastases to provide an overview of the current research progress. Exciting progress has been made by focusing on specific mutations within lung cancer, including the use of EGFR tyrosine kinase inhibitors or inhibitors for anaplastic lymphoma kinase gene rearrangement, such as osimertinib, alectinib, and lorlatinib. These targeted therapies have shown impressive results in penetrating the central nervous system (CNS). Regarding whole-brain radiotherapy, there is currently some controversy among investigators regarding its effect on survival. Additionally, immune checkpoint inhibitors (ICIs) have demonstrated reliable clinical benefits due to their ability to retain anticancer activity in CNS metastases. Moreover, combination therapy shows promise in providing further treatment possibilities. Considerable progress has been made in the clinical research of lung cancer with LM. However, the sample size of prospective clinical trials investigating LM for lung cancer is still limited, with most reports being retrospective. Developing more effective management protocols for metastatic LM in lung cancer remains an ongoing challenge for the future.

The FJQR Has Synergistic Effect with Fluoropyrimidine in the Maintenance Treatment for HER-2 Negative Gastric Cancer.

INTRODUCTION: Maintenance therapy aimed to strengthen the first-line chemotherapy and improve quality of life is needed for gastric cancer (GC). Currently, many clinical studies have confirmed the important role of fluoropyrimidine in the maintenance stage. Our team has created patented prescriptions "Fuzheng jiedu Quyu Method" recipe (FJQR), which was considered as an adjuvant therapeutic scheme (reduce toxicity and increase the efficacy of chemotherapy). This study aimed to evaluate the efficacy and safety of FJQR combined with fluoropyrimidine as a maintenance treatment in HER-2 negative GC patients. METHODS: We performed the analysis of 129 patients with HER-2 negative GC who entered the maintenance stage in our hospital and Tianjin Cancer Hospital between January 2018 and December 2020. Out of the 129 eligible patients, 64 were categorized into the maintenance treatment group with FJQR+fluoropyrimidine, and 65 patients were assigned to the control group if they received fluoropyrimidine alone. Capecitabine was orally 1000mg/m2, Qd, half an hour after meals, and FGQR was 15g Bid after capecitabine. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), overall remission rate (ORR), quality of Life (QOL), TCM syndrome and safety. RESULTS: The mPFS in the treatment group was significantly prolonged compared with the control group (6.3 vs. 5.0 months, p = 0.03), while the mOS was not substantially improved (11.4 vs. 10.5 months, p = 0.38). Gastrointestinal symptoms and pain became better in the treatment group. The number of distant metastatic organs, first-line chemotherapy cycles, and lymph node metastasis were independent risk predictors for PFS. Blood stasis syndrome may be the protective factor. In terms of safety, treatment-related adverse events (AEs) in the treatment group were relatively lighter, and the incidence of grade III-IV AEs could be significantly reduced. CONCLUSION: FJQR and fluoropyrimidine have synergistic effects as maintenance treatment in HER-2 negative GC, with good efficacy and safety.

Clinical efficacy of Camrelizumab combined with first-line chemotherapy in extensive-stage small-cell lung cancer.

Objective: Exploring the clinical efficacy of camrelizumab in combination with first-line chemotherapy in patients with extensive-stage small-cell lung cancer (ES-SCLC). Methods: The clinical data of 35 patients with ES-SCLC who received camrelizumab combined with EC or EP regimen in First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from January 2020 to January 2023 were retrospectively analyzed. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were OS, ORR and DCR. SPSS 25.0 software was used for statistical analysis, Kaplan-Meier curve and Log-Rank test analysis, and survival curve was drawn. Results: The median PFS of 35 patients with SCLC was 7.4 months (95 % CI 6.75-9.81 months), .and the median OS was 12.5 months (95% CI,11.71-16.90 months). The ORR and DCR were 65.7 % and 74.3 %, respectively. Adverse events (AEs) were mainly concentrated in grade 1-2, and the probability of occurrence of grade 3 or above was low. Reactive Cutaneous Capillary Endothelial Proliferation (RCCEP) was the most common, followed by nausea &vomit and anemia. The other common AEs included abnormal thyroid function, decreased neutrophil count, skin rash and leucopenia. Conclusion: Camrelizumab in combination with first-line chemotherapy regimens prolonged OS and PFS in SCLC patients and showed efficacy and safety in real-world data.

ADCY4 promotes brain metastasis in small cell lung cancer and is associated with energy metabolism.

Brain metastasis (BMs) in small cell lung cancer (SCLC) has a very poor prognosis. This study combined WGCNA with the mfuzz algorithm to identify potential biomarkers in the peripheral blood of patients with BMs. By comparing the significantly differentially expressed genes present in BMs samples, we identified ADCY4 as a target for further study. Expression of ADCY4 was used to cluster mfuzz expression pattern, and 28 hub genes for functional enrichment. PPI network analysis were obtained by comparing with differentially expressed genes in BMs. GABRE, NFE4 and LMOD2 are highly expressed in patients with BMs and have a good diagnostic effect. Immunoinfiltration analysis showed that SCLC patients with BMs may be associated with memory B cells, Tregs, NK cell activation, macrophage M0 and dendritic cell activation. prophytic was used to investigate the ADCY4-mediated anti-tumor drug response. In conclusion, ADCY4 can be used as a promising candidate biomarker for predicting BMs, molecular and immune features in SCLC. PCR showed that ADCY4 expression was increased in NCI-H209 and NCI-H526 SCLC cell lines. In vitro experiments confirmed that the expression of ADCY4 was significantly decreased after anti-PD1 antibody treatment, while the expression of energy metabolism factors were significantly different. This study reveals a potential mechanism by which ADCY4 mediates poor prognosis through energy metabolism -related pathways in SCLC.

Research progress on the immunomodulatory mechanism of acupuncture in tumor immune microenvironment.

With the constantly deeper understanding of individualized precision therapy, immunotherapy is increasingly developed and personalized. The tumor immune microenvironment (TIME) mainly consists of infiltrating immune cells, neuroendocrine cells, extracellular matrix, lymphatic vessel network, etc. It is the internal environment basis for the survival and development of tumor cells. As a characteristic treatment of traditional Chinese medicine, acupuncture has shown potentially beneficial impacts on TIME. The currently available information demonstrated that acupuncture could regulate the state of immunosuppression through a range of pathways. An effective way to understand the mechanisms of action of acupuncture was to analyze the response following treatment of the immune system. This research reviewed the mechanisms of acupuncture regulating tumor immunological status based on innate and adaptive immunity.

Research progress of antibody-drug conjugates therapy for HER2-low expressing gastric cancer.

Gastric cancer (GC) is a highly fatal malignant tumor in the world. Most of the patients are in an unresectable state when they have symptoms. Systemic treatment is the primary treatment for advanced patients. Among them, the Human epidermal growth factor receptor 2 (HER2) is an important therapeutic target. With the continuous optimization of chemotherapeutic drugs and chemotherapy regimens, the prognosis of some HER2-positive GC patients has been greatly improved. However, the needs of GC patients with a low level of HER2 expression still need to be met. Several targeted drugs against human epidermal growth factor receptor 2 emerged in recent years, including Antibody-drug Conjugates (ADC), novel humanized anti-HER2 monoclonal antibodies, and Tyrosine kinase inhibitors (TKI). As an important breakthrough in treating HER2-positive GC, ADC became one of the fastest-growing anti-tumor drugs. Some drugs also showed an anti-tumor effect on GC with low expression of HER2. It may also be the key to the treatment of low expression of HER2 GC in the future. This article mainly reviews several promising ADC drugs for the treatment of HER2 low-expression GC and related trials.

A comprehensive overview of the relationship between RET gene and tumor occurrence.

RET gene plays significant roles in the nervous system and many other tissues. Rearranged during transfection (RET) mutation is related to cell proliferation, invasion, and migration. Many invasive tumors (e.g., non-small cell lung cancer, thyroid cancer, and breast cancer) were found to have changes in RET. Recently, great efforts have been made against RET. Selpercatinib and pralsetinib, with encouraging efficacy, intracranial activity, and tolerability, were approved by the Food and Drug Administration (FDA) in 2020. The development of acquired resistance is inevitable, and a deeper exploration should be conducted. This article systematically reviewed RET gene and its biology as well as the oncogenic role in multiple cancers. Moreover, we also summarized recent advances in the treatment of RET and the mechanism of drug resistance.

A novel long noncoding RNA (lncRNA), LINC02657(LASTR), is a prognostic biomarker associated with immune infiltrates of lung adenocarcinoma based on unsupervised cluster analysis.

Non-small cell lung cancer (NSCLC) has long been the deadliest malignancy worldwide, with adenocarcinoma (AD) being the most common pathological subtype. Here we focused on the value of LASTR in LUAD. Using expression analysis, enrichment analysis, immune cell infraction analysis, we found that the expression level of LASTR was significantly increased in LUAD tissue. Meanwhile, LASTR was significantly associated with differential infiltration of various immune cells. Kaplan-Meier survival analysis showed that LUAD related with a poor prognosis in terms of OS, PFI, and DSS compared with high-expression LASTR. The enrichment analysis showed that LASTR is related to the pathays like PI3K-AKT signaling pathway. Thus, the present findings could be helpful in a better understand of LASTR in LUAD. RT-PCR was used to verify the high expression of LASTR in LUAD tissues, and the apoptosis of LUAD cell lines was promoted by CCK8 and Transwell experiments to verify the ability of LASTR to promote the migration and invasion of lung cancer cells in vitro.

Liver-Targeting Composite Nanocarrier Delivery System Based on Chitosan Nanoparticles and Phospholipid Complexes.

Liver fibrosis is mainly caused by excessive accumulation of extracellular matrix and structural changes in the liver, ultimately leading to cirrhosis if left untreated. Reducing hyaluronan synthesis by inhibiting hyaluronic acid deposition or regulating the expression of hyaluronic synthase can ameliorate liver fibrosis symptoms. In this study, we aimed to improve the bioavailability and liver-targeting capacity of hydroxymethyl coumarin (4-MU) using a newly developed phospholipid complex chitosan nanoparticle (4-MU PC/CNP) optimized using the Box-Behnken design. The composite nanocarrier delivery system was formulated using solvent evaporation technology, and formulation and process parameters were evaluated. Furthermore, 4-MU PC/CNPs and their pharmacokinetics were characterized. The established 4-MU PC/CNPs had an average particle size of 153.07 ± 0.29 nm, a polydispersity index value of 0.383, and a positive zeta potential of ∼35.4 mV. Compared with 4-MUs, 4-MU PC/CNPs exhibited significantly improved water solubility, faster plasma clearance and tissue distribution, and better liver targeting. Pharmacokinetic analysis showed that the oral bioavailability of 4-MU in 4-MU PC/CNPs was significantly higher than that of simple 4-MU. In conclusion, 4-MU PC improved drug lipid (oil-water distribution coefficient of 1.31 ± 0.03) and water solubilities (2.05 times the drug substance). 4-MU PC/CNPs significantly improved 4-MU oral bioavailability, representing a promising approach for enhancing drug solubility. This study demonstrates that the targeting parameters of 4-MU PC/CNPs in the liver were all greater than 1, indicating that they specifically targeted the liver, thereby potentially alleviating liver fibrosis.

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.

Clinical research progress on BRAF V600E-mutant advanced colorectal cancer.

Colorectal cancer is one of the malignant tumors that pose a serious threat to human health. A particularly bad prognosis might be expected for colorectal tumors with the unique molecular subtype BRAF V600E mutation. With the development of precision therapy, the advent of molecularly targeted therapies and immune checkpoint inhibitors has improved the outcome of intermediate to advanced colorectal cancer. However, the duration of drug benefit is usually short, and overall survival and progression-free survival remain suboptimal. Therefore, investigators are exploring more rational, safe, and effective drug combination regimens through clinical trials to provide longer survival for patients with such genetic mutations with metastatic colorectal cancer (mCRC). This article reviews the progress of clinical research on molecularly targeted drugs, immune checkpoint inhibitors, first-line chemotherapeutic agents, and different combination therapy regimens (including different targeted drug combinations, immune combination targeting, and chemotherapy combination targeting) for colorectal cancer patients with BRAF V600E mutation, which provides a reference for further in-depth clinical exploration of the treatment of colorectal cancer patients with BRAF V600E mutation.