A molecular approach to triple-negative breast cancer: targeting the Notch signaling pathway

ABSTRACT Introduction Triple-negative breast cancer is an aggressive subtype of breast cancer characterized by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression. This phenotype renders triple-negative breast cancer cells refractory to conventional therapies, resulting in poor clinical outcomes and an urgent need for novel therapeutic approaches. Recent studies have implicated dysregulation of the Notch receptor signaling pathway in the development and progression of triple-negative breast cancer. Objective This study aimed to conduct a comprehensive literature review to identify potential therapeutic targets of the Notch pathway. Our analysis focused on the upstream and downstream components of this pathway to identify potential therapeutic targets. Results Modulating the Notch signaling pathway may represent a promising therapeutic strategy to treat triple-negative breast cancer. Several potential therapeutic targets within this pathway are in the early stages of development, including upstream (such as Notch ligands) and downstream (including specific molecules involved in triple-negative breast cancer growth). These targets represent potential avenues for therapeutic intervention in triple-negative breast cancer. Comments Additional research specifically addressing issues related to toxicity and improving drug delivery methods is critical for the successful translation of these potential therapeutic targets into effective treatments for patients with triple-negative breast cancer.

Seguridad de las drogas biológicas y sintéticas dirigidas utilizadas en pacientes con enfermedades reumáticas inmunomediadas. Datos del registro BIOBADASAR 3.0 / Safety of biological and targeted synthetic drugs in patients with immune-mediated rheumatic diseases. Data from the BIOBADASAR 3.0 registry

Introducción: conocer la seguridad de las drogas actualmente disponibles para el tratamiento de las enfermedades reumáticas es muy importante al momento de tomar decisiones terapéuticas objetivas e individualizadas en la consulta médica diaria. Asimismo, datos de la vida real amplían el conocimiento revelado por los ensayos clínicos. Objetivos: describir los eventos adversos (EA) reportados, estimar su frecuencia e identificar los factores relacionados con su desarrollo. Materiales y métodos: se utilizaron datos BIOBADASAR, un registro voluntario y prospectivo de seguimiento de EA de tratamientos biológicos y sintéticos dirigidos en pacientes con enfermedades reumáticas inmunomediadas. Los pacientes son seguidos hasta la muerte, pérdida de seguimiento o retiro del consentimiento informado. Para este análisis se extrajeron datos recopilados hasta el 31 de enero de 2023. Resultados: se incluyó un total de 6253 pacientes, los cuales aportaron 9533 ciclos de tratamiento, incluyendo 3647 (38,3%) ciclos sin drogas modificadoras de la enfermedad biológicas y sintéticas dirigidas (DME-b/sd) y 5886 (61,7%) con DME-b/sd. Dentro de estos últimos, los más utilizados fueron los inhibidores de TNF y abatacept. Se reportaron 5890 EA en un total de 2701 tratamientos (844 y 1857 sin y con DME-b/sd, respectivamente), con una incidencia de 53,9 eventos cada 1000 pacientes/año (IC 95% 51,9-55,9). La misma fue mayor en los ciclos con DME-b/sd (71,1 eventos cada 1000 pacientes/año, IC 95% 70,7-77,5 versus 33,7, IC 95% 31,5-36,1; p<0,001). Las infecciones, particularmente las de la vía aérea superior, fueron los EA más frecuentes en ambos grupos. El 10,9% fue serio y el 1,1% provocó la muerte del paciente. El 18,7% de los ciclos con DME-b/sd fue discontinuado a causa de un EA significativamente mayor a lo reportado en el otro grupo (11,5%; p<0,001). En el análisis ajustado, las DME-b/sd se asociaron a mayor riesgo de presentar al menos un EA (HR 1,82, IC 95% 1,64-1,96). De igual manera, la mayor edad, el mayor tiempo de evolución, el antecedente de enfermedad pulmonar obstructiva crónica, el diagnóstico de lupus eritematoso sistémico y el uso de corticoides se asociaron a mayor riesgo de EA. Conclusiones: la incidencia de EA fue significativamente superior durante los ciclos de tratamientos que incluían DME-b/sd.

Introduction: knowing the efficacy and safety of the drugs currently available for the treatment of rheumatic diseases is very important when making objective and individualized therapeutic decisions in daily medical consultation. Likewise, real-life data extends the knowledge revealed by clinical trials. Objectives: to describe the reported adverse events (AEs), estimate their frequency and identify factors associated to them. Materials and methods: BIOBADASAR data were used, which is a voluntary, prospective follow-up registry of AEs of biological and synthetic treatments in patients with immune-mediated rheumatic diseases. Patients are followed until death, loss of followup, or withdrawal of informed consent. To carry out this analysis, the data collected up to January 31, 2023 was extracted. Results: a total of 6253 patients were included, who contributed with 9533 treatment periods, including 3647 (38.3%) periods without b/ts-DMARDs and 5886 (61.7%) with b/ts-DMARDs. Among the latter, the most used were TNF inhibitors and abatacept. A total of 5890 AEs were reported in a total of 2701 treatments (844 and 1857 without and with b/ts-DMARDs, respectively), with an incidence of 53.9 events per 1000 patients/ year (95% CI 51.9-55.9). It was higher during the periods with b/ts-DMARDs (71.1 events per 1000 patients/year, 95% CI 70.7-77.5 vs 33.7, 95% CI 31.5-36.1, p<0.001). Infections, particularly those of the upper respiratory tract, were the most frequent AEs in both groups. 10.9% were severe and 1.1% were associated with the death of the patient. 18.7% of the periods with b/ts-DMARDs were discontinued due to an AE, significantly higher than that reported in the other group (11.5%; p<0.001). In the adjusted analysis, b/ts-DMARDs were associated with a higher risk of presenting at least one AE (HR 1.82, 95% CI 1.64-1.96). Similarly, older age, longer evolution time, history of chronic obstructive pulmonary disease, diagnosis of systemic lupus erythematosus, and use of corticosteroids were associated with a higher risk of AE. Conclusions: the incidence of AEs was significantly higher during those treatment periods that included DME-b/sd.

Clinical efficacy and pharmacoeconomic evaluation of bevacizumab or cetuximab combined with chemotherapy in the treatment of advanced colorectal cancer / 中国医师进修杂志

Objective:To compare the clinical efficacy and pharmacoeconomic evaluation of bevacizumab or cetuximab combined with chemotherapy in the treatment of advanced colorectal cancer.Methods:The clinical data of 68 patients with advanced colorectal cancer from January 2018 to December 2020 in Baotou Tumor Hospital were retrospectively analyzed. Among them, 40 patients with treated with bevacizumab combined with chemotherapy (bevacizumab group), 28 patients were treated with cetuximab combined with chemotherapy (cetuximab group), and the chemotherapy of two group was FOLFOX/FOLFIRI program. The short-term clinical efficacy, adverse reactions and pharmacoeconomic evaluation result were compared between two groups.Results:There were no statistical differences in effective rate and disease control rate between bevacizumab group and cetuximab group: 30.00% (12/40) vs. 28.57% (8/28) and 67.5% (27/40) vs. 60.71% (17/28), P>0.05. The incidence of Ⅲ to Ⅳ grade erythra in bevacizumab group was significantly lower than that in cetuximab group: 2.50% (1/40) vs. 71.43% (20/28), and there was statistical difference ( P<0.01); there were no statistical differences in the incidences of Ⅲ to Ⅳ grade bone marrow suppression, nausea vomiting, hepatic functional lesion and diarrhea between two groups ( P>0.05). The pharmacoeconomic evaluation result showed that the cost of monoclonal antibody and total cost in bevacizumab group were significantly lower than those in cetuximab group: (9 009 ± 1 500) yuan vs. (27 840 ± 2 202) yuan and (11 242 ± 1 731) yuan vs. (29 867 ± 3 002) yuan, and there were statistical differences ( P<0.01); the cost-effectiveness ratio in bevacizumab group was 37 473.3, and it in cetuximab group was 104 430.1, the incremental cost-effectiveness ratio of two programs was 11 640.6. Conclusions:In the treatment of advanced colorectal cancer, the efficacy of bevacizumab combined with chemotherapy is similar to that of cetuximab combined with chemotherapy, but bevacizumab combined with chemotherapy has lower costs and fewer adverse reactions, so bevacizumab is more economical and applicable.

Value of normalized apparent diffusion coefficient in predicting HER2 expression in bladder cancer / 现代泌尿外科杂志

【Objective】 To predict the expression of human epidermal growth factor receptor 2 (HER2) in urothelial bladder carcinoma based on normalized apparent diffusion coefficient (ADC). 【Methods】 The preoperative pelvic 3.0T magnetic resonance imaging (MRI) images of 127 patients with urothelial bladder carcinoma were retrospectively studied, the ADC was measured, and the HER2 expression in postoperative tissue specimens was determined with immunohistochemistry (IHC). The differences in normalized ADC were analyzed among different HER2 expressions and among different expression divisions. Correlation between normalized ADC and HER2 expression was analyzed. The optimal diagnostic threshold for distinguishing different expression divisions were determined with receiver operating characteristic (ROC) curve. 【Results】 Normalized ADC was negatively correlated with HER2 expression (tau-b=-0.180, P=0.008). Normalized ADC of HER2 overexpression group (IHC 2+, 3+) was lower than that of HER2 negative group (IHC 0, 1+) (P=0.081). Normalized ADC of HER2 expression group (IHC 1+, 2+, 3+) was significantly lower than that of HER2 zero-expression group (IHC 0) (P=0.020). Normalized ADC of HER2 strong positive group (IHC 3+) was significantly lower than that of HER2 non-strong positive group (IHC 0, 1+, 2+) (P=0.024). The optimal diagnostic threshold of HER2 strong positive group was 0.849; the sensitivity, specificity and accuracy were 0.621, 0.909 and 0.765, respectively. The optimal diagnostic threshold of HER2 overexpression group was 0.909; the sensitivity, specificity and accuracy were 0.547, 0.667 and 0.607, respectively. 【Conclusion】 Normalized ADC is negatively correlated with HER2 expression. ADC may be a potential marker for predicting HER2 expression.

Advances in the protective mechanism and clinical implications of autophagy in liver failure / 临床肝胆病杂志

‍Liver failure is a serious clinical syndrome of liver disease with critical condition and high mortality， and besides liver transplantation， there is still a lack of satisfactory radical treatment methods. The pathogenesis of liver failure is complex and remains unclear， involving a variety of factors that affect the balance of hepatocyte necrosis and regeneration. This article summarizes autophagy as the key pathway for maintaining cell homeostasis and points out that autophagy plays an important protective role in the pathogenesis of liver failure by regulating NLRP3 inflammasome activation， reducing oxidative stress， and inhibiting cell apoptosis. Meanwhile， it is believed that the molecular signaling pathways targeting autophagy， such as exosomes and peroxisome proliferator－activated receptor α， participate in antagonizing the development and progression of liver failure and will become important ideas and directions for molecular targeted therapies for liver failure.

Progress of immunotherapy strategies for uveal melanoma / 肿瘤研究与临床

Uveal melanoma (UM) is the most common intraocular malignancy in adults. Recently, great progresses have been made in the diagnosis, treatment and prognosis of UM, however, nearly 50% of patients still develop liver metastases, which severely affects on the survival of UM patients. Whether UM patients will benefit from the immune checkpoint blockade similarly as the cutaneous melanoma (CM)? Whether the specific gene mutations targeting UM could improve the anti-tumor efficacy? Whether chimeric antigen receptor T cell or T cell receptor T cell immunotherapy is effective to UM patients with liver metastases? How about the combinational therapies in UM and the clinical effects? This review summarizes the anti-tumor research and novel treatment options of UM, analyzes the current achievements and problems.

Progress of molecular targeted therapy for adenoid cystic carcinoma of salivary gland / 肿瘤研究与临床

Adenoid cystic carcinoma (ACC) is a salivary gland malignant tumor which mainly occurs in the head, neck and the mammary gland, and is characterized with easy invasion of peripheral nerves, local easy recurrence after resection and painless distant metastasis. The treatment of ACC is usually based on surgical resection combined with postoperative radiotherapy. Patients with advanced disease usually cannot be cured, so far there is no ideal treatment regimen. Some studies have suggested that some targeted drugs show advantages in ACC patients who are insensitive or resistant to conventional therapy. This paper summarizes the research progress of molecular targeted therapy for ACC of salivary gland in order to provide new treatment options for ACC patients especially for those at advanced stage.

Progress of epidermal growth factor receptor-tyrosine kinase inhibitors in treatment of operable non-small cell lung cancer / 肿瘤研究与临床

Patients with operable non-small cell lung cancer (NSCLC) receiving neoadjuvant or adjuvant chemotherapy have a very limited improvement in 5-year survival rate. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) have made a breakthrough in the treatment of EGFR-mutant advanced NSCLC, which shed light for the exploration of perioperative targeted therapy in NSCLC patients. Significant progress has been made in the research of targeted therapy of the first and third generation EGFR-TKI in perioperative patients. The availability of novel potent and less toxic targeted therapy has brought new treatments for the operable NSCLC. This article reviews the progress and existing problems of adjuvant and neoadjuvant targeted therapy in NSCLC harboring EGFR mutation.

Progress of adipokines in cancer treatment / 肿瘤研究与临床

Obesity is a well-known high-risk factor for many kinds of neoplasms. Adipokines secreted by adipose tissue play an important role in the process of obesity promoting tumorigenesis and development, and different adipokines play a role in promoting or suppressing cancer via different signaling pathways. Currently, lifestyle modification to control weight and targeted therapy of adipokines and their receptors are major research directions of cancer treatment, but most of the studies are still in the stage of basic and pre-clinical research. Therefore, the molecular mechanisms of adipokines in promoting or suppressing cancer should be further explored, and the dual inhibitors as well as combined therapy are the key research strategies for adipokines in cancer treatment in the future.

Renal thrombotic microangiopathy induced by targeted therapy combined with immunotherapy: a case report / 中华肾脏病杂志

Targeted therapy and immunotherapy have achieved great success in treating various solid and non-solid tumors, but the incidence of drugs-related adverse events is relatively high. The paper reports a case of renal thrombotic microangiopathy in an intrahepatic cholangiocarcinoma patient who underwent targeted therapy combined with immunotherapy. During the treatment, the tumor burden relieved continuously, but the patient developed proteinuria, edema and hypertension. The ADAMTS13 activity and inhibitors were normal, while the antiphospholipid antibody was positive. The patient was finally diagnosed as glomerular thrombotic microangiopathy with immune complex deposition by renal biopsy. After the cease of the antineoplastic agents and treatment with "cordyceps preparations" and "α-keto acids", the patient's blood pressure dropped to normal, her urine protein turnned to weakly positive, and her renal function remained stable.

Function and regulatory mechanism of androgen receptor variant 7 in castration resistant prostate cancer / 中华泌尿外科杂志

Androgen receptor (AR) plays a key regulatory role in the development of castration resistant prostate cancer (CRPC), and the level of constitutive active variants represented by androgen receptor variant 7 (AR-V7) is increasing during the progress of CRPC, which can be used as a molecular marker of disease progress and prognosis of patients with CRPC. It is an important target to overcome castration resistance and improve the quality of life and survival of patients. In this paper, the function of AR-V7 and its molecular regulation mechanism in CRPC are reviewed. The research shows that the generation of AR-V7 is related to the structural rearrangement of AR gene, gene amplification and the selective splicing of AR gene transcripts, and it is affected by the coordinated regulation of multiple signal pathway molecules such as TGF-β; AR-V7 changes the transport and nuclear localization mechanism of AR protein, and further affects the transcriptional expression of downstream target genes. AR-V7 antagonizes AR activity and blocks the differentiation process driven by AR and androgen, and inhibits the expression of tumor suppressor genes to stimulate the proliferation of tumor cells, thus promoting the progress of Pca. Related targeting studies have revealed AR-V7 targets and CRPC treatment strategies. Currently, they mainly focus on AR-V7 protein degradation, mRNA expression inhibition and N-terminal domain targeting intervention. With the development of in-depth research, the molecular mechanism of AR-V7 in the progress of Pca will be gradually clarified, which will certainly play a greater role in the prevention and treatment of CRPC.

Efficacy and safety analysis of anlotinib in the treatment of distant metastatic radioactive iodine-refractory differentiated thyroid cancer / 中华核医学与分子影像杂志

Objective:To investigate the efficacy and safety of anlotinib in distant metastatic radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC).Methods:Retrospective analysis was performed on 17 patients with distant metastatic RAIR-DTC (6 males, 11 females, age: 57.0(45.5, 63.0) years) from Affiliated Hospital of Qingdao University between October 2018 and February 2023, including 13 patients receiving first-line treatment and 4 patients receiving second-line treatment with anlotinib. The changes of serum thyroglobulin (Tg) during the treatment of anlotinib, the changes of maximum diameter of the target lesion at the last follow-up compared with the diameter at baseline, the imaging efficacy, and treatment-related adverse events were analyzed. The serological and imaging effects of the first-line treatment group and the second-line treatment group were compared. The Fisher exact test was used to analyze the differences between groups.Results:The follow-up time of 17 patients was 17.3(9.5, 21.4) months, and the objective response rate (ORR) and disease control rate (DCR) were 7/17 and 16/17, respectively. There were no significant differences of ORR (6/13 vs 1/4; P=0.603) and DCR (13/13 vs 3/4; P=0.235) between the first-line and second-line treatment groups. The change rates of serum Tg at 3, 6 weeks and the last follow-up were -30.2%(-61.2%, -15.5%), -64.8%(-90.6%, -32.3%), and -85.8%(-96.1%, -50.7%), respectively. At the last follow-up, the change rate of maximum diameter of target lesions was -20.0%(-45.0%, -5.2%). The incidence of treatment-related adverse reactions was 14/17, and 2 patients (2/17) had grade 3 or above adverse reactions. Conclusion:Anlotinib shows superior efficacy with tolerable toxicity in the first-line treatment of distant metastatic RAIR-DTC, and hopefully plays an important role in second-line treatment for RAIR-DTC resistant to sorafenib.

Connexin 43: A new therapeutic target against blinding eye diseases / 国际眼科杂志(Guoji Yanke Zazhi)

The major blinding eye diseases, such as keratitis, cataract, glaucoma, diabetic retinopathy, seriously threaten human health and affect the quality of patients' life. Connexin 43(Cx43), as the most common connexin in vertebrates, is widely distributed in eye tissues and is involved in physiological processes such as embryonic development, metabolic regulation, tissue homeostasis, as well as pathological processes such as inflammation, oxidative stress, epithelial-mesenchymal transition, vascular leakage, and angiogenesis. Cx43 plays an important role in the occurrence and development of various blinding eye diseases. This article will review its role in the pathogenesis of the above-mentioned blinding eye diseases and the advances in targeting Cx43 therapy.

Research advances in transcatheter arterial chemoembolization combined with targeted agents or anti-PD-1/PD-L1 monoclonal antibody in treatment of patients with unresectable hepatocellular carcinoma / 临床肝胆病杂志

Transcatheter arterial chemoembolization (TACE) is recommended by domestic and international guidelines for the treatment of patients with unresectable hepatocellular carcinoma (uHCC), and it is one of the most common treatment methods for patients with uHCC. The chemotherapy drugs commonly used in TACE for HCC include epirubicin, cisplatin, and fluorouracil, while it is still unclear which chemotherapy drug has a better clinical effect. This article summarizes the studies of different TACE regimens using different chemotherapy drugs in the treatment of patients with uHCC in the recent five years. TACE combined with sorafenib can significantly improve the survival of patients with advanced HCC and has been recommended for the treatment of such patients by Chinese Society of Clinical Oncology guidelines, and the efficacy of TACE combined with other tyrosine kinase inhibitors (TKI) has become a research hotspot. Studies have shown that compared with TACE combined with sorafenib in the treatment of patients with advanced HCC, TACE combined with lenvatinib can achieve a significantly longer progression-free survival time and a tendency of increase in median overall survival time. However, due to the variation of target receptors or downstream signals, resistance to molecular-targeted agents is still a challenging problem. TKI combined with immune checkpoint inhibitors may be a promising strategy for the treatment of patients with uHCC. Some studies suggest that triple therapy using TACE combined with TKIs and anti-PD-1/PD-L1 monoclonal antibody has better efficacy in improving the survival of patients with uHCC. This article reviews the studies of the efficacy and safety of TACE combined with targeted agents and TACE combined with anti-PD-1/PD-L1 monoclonal antibody in the treatment of patients with uHCC in the recent five years.

Efficacy of hepatic arterial infusion chemotherapy and its multimodality therapeutic regimens in treatment of patients with advanced hepatocellular carcinoma and related prognostic factors / 临床肝胆病杂志

Objective To investigate the efficacy of continuous hepatic arterial infusion chemotherapy (HAIC) with the FOLFOX regimen and its multimodality therapeutic regimen in the treatment of patients with advanced hepatocellular carcinoma, as well as the influencing factors for prognosis. Methods A retrospective analysis was performed for the clinical data of 66 patients with advanced hepatocellular carcinoma who received continuous HAIC with FOLFOX regimen in Nanfang Hospital, Southern Medical University, from September 2018 to November 2021. The patients were observed in terms of objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), and median overall survival (mOS) after treatment, and treatment-related adverse reactions were recorded. For the patients with portal vein tumor thrombus, the effect of the treatment on portal vein tumor thrombus was assessed. The Kaplan-Meier method was used for survival analysis, and the Cox regression analysis was used to investigate the influencing factors for prognosis. Results According to the RECIST1.1 criteria, FOLFOX-HAIC and its multimodality therapeutic regimen achieved an ORR of 33.3% (22/66) and a DCR of 86.4% (57/66) in the treatment of 66 patients with advanced hepatocellular carcinoma, with an mPFS time of 8.2 months and an mOS time of 22.1 months. Among the 39 patients with portal vein tumor thrombus, 2 achieved complete remission, 8 achieved partial remission, 24 achieved stable disease, and 5 had disease progression, with an ORR of 25.6% (10/39) and a DCR of 87.2% (34/39). The main adverse reactions included gastrointestinal reactions (16.7%, 11/66), pyrexia (12.1%, 8/66), liver area pain (10.6%, 7/66), bone marrow suppression (3.0%, 2/66), and contrast agent allergy (3.0%, 2/66), and there were no grade > Ⅳ toxic or side effects or deaths caused by such complications. The Cox regression analysis showed that extrahepatic metastasis (hazard ratio [ HR ]=2.668, 95% confidence interval [ CI ]: 1.357-5.245, P < 0.05) and prothrombin time (PT) ( HR =1.282, 95% CI : 1.080-1.630, P < 0.05) were independent risk factors for PFS, and aspartate aminotransferase level ( HR =1.008, 95% CI : 1.002-1.013, P < 0.05) and PT ( HR =1.303, 95% CI : 1.046-1.630, P < 0.05) were independent risk factors for OS. Conclusion FOLFOX-HAIC and its multimodality therapeutic regimen has a certain clinical effect with controllable adverse reactions in the treatment of advanced hepatocellular carcinoma.

Research advances in tumor-associated macrophages in hepatocellular carcinoma microenvironment / 临床肝胆病杂志

Since there is a lack of obvious clinical symptoms in the early stage of hepatocellular carcinoma (HCC), most patients have progressed to the advanced stage at the time of confirmed diagnosis. There are limited treatment options for HCC patients who miss the opportunity for surgery, so it is of great importance to find new therapeutic targets. Tumor-associated macrophages (TAMs) are a group of macrophages existing in the tumor immune microenvironment and affect the malignant behaviors of HCC cells and the state of immune escape within the tumor. This article introduces the origin and classification of TAM, summarizes the role and mechanism of TAMs in vascular proliferation, invasion and metastasis, formation and maintenance of stemness, and anti-tumor immunity in HCC, and briefly describes the current research advances in therapeutic targets for TAM, and it is pointed out that targeting TAM may be a promising direction for clinical treatment.

Research advances in immunotherapy for hepatocellular carcinoma / 临床肝胆病杂志

Hepatocellular carcinoma (HCC) has an insidious onset, and most patients are in the advanced stage when attending the hospital and thus lose the opportunity for radical surgical resection, which results in the poor prognosis of patients. With the development of clinical treatment, the treatment of advanced HCC has gradually transitioned from the relatively single and limited treatment options in the past to the new model of comprehensive treatment. In recent years, immunotherapy, represented by immune checkpoint inhibitors (ICIs), has become widely used in clinical practice. At present, a number of clinical studies have been conducted for immunotherapy combined with local and targeted antitumor therapy, and in particular, ICIs combined with targeted therapy have become a research hotspot in the field of HCC treatment. This article reviews the research advances in immunotherapy for the treatment of HCC.

Role of new potential immune blocking molecules in the development and progression of hepatocellular carcinoma / 临床肝胆病杂志

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors around the world. The emergence of immune checkpoint inhibitors targeting programmed death-1/programmed death-ligand 1 and cytotoxic T lymphocyte-associated antigen-4 has brought great breakthroughs in the treatment of HCC. However, since HCC is a type of tumor with high heterogeneity, monotherapy is only effective for a small number of patients and may not be able to achieve long-lasting benefits due to drug resistance, and therefore, it is necessary to explore the potential of new immune checkpoint inhibitors in the prevention and treatment of HCC. This article analyzes and summarizes the biological characteristics of the new immune checkpoints T cell immunoglobulin and ITIM domain (TIGIT), V-domain immunoglobulin suppressor of T-cell activation (VISTA), B and T lymphocyte attenuator (BTLA), and B7 homologous protein-4 (B7-H4) and their expression and function in HCC. The analysis shows that TIGIT, VISTA, BTLA, and B7-H4 are highly expressed in HCC tissue and are associated with the prognosis of HCC patients, and targeted blocking of corresponding pathways can effectively inhibit the progression of HCC, suggesting that these molecules are potential targets for tumor treatment and that in-depth studies can provide new directions for HCC immunotherapy.

Progress of PARP inhibitors in targeted therapy of small cell lung cancer / 国际肿瘤学杂志

Small cell lung cancer (SCLC) is a rapidly developing malignant tumor, which is highly heterogeneous and prone to drug resistance, and the prognosis is usually poor. Poly ADP-ribose polymerase (PARP) inhibitors target the DNA damage response pathway, preventing DNA repair, thereby exerting anti-tumor effects. Currently, PARP inhibitors are used as monotherapy or in combination with DNA-damaging agents or immune checkpoint inhibitors in the treatment of SCLC. Although the current research results are limited, it can be seen that PARP inhibitors may be a breakthrough in the targeted therapy of SCLC.

Research progress on the application of combining radiotherapy and systemic therapy in breast cancer / 国际肿瘤学杂志

Compared with single therapy, radiotherapy combined with chemotherapy, endocrine therapy, molecular targeted therapy and immunological therapy can not only shorten the treatment cycle, but also improve the local control rate and prolong the survival of patients. However, the safety of combined therapy still needs to be further clarified to comprehensively evaluate the feasibility. Therefore, exploring the efficacy and safety of radiotherapy combined with systematic therapy will provide evidence for clinical benefits.