scholarly journals Prospects of application of inhibitors of PD-1/PD-L1 checkpoints in malignant tumors of the stomach and esophagogastric junction

2020 ◽  
pp. 15-21
Author(s):  
D. D. Sakaeva ◽  
A. A. Melnikova
Keyword(s):  
Esophagogastric Junction ◽  
Kinase Inhibitors ◽  
Malignant Tumors ◽  
Checkpoint Inhibitors ◽  
Combined Therapy ◽  
Therapy Response ◽  
Treatment Method ◽  
Tumor Tissues ◽  
Advanced Stages

Malignant tumors of the stomach and esophagogastric junction in advanced stages progress quite aggressively, and the prospects for treatment of these patients remain unpromising. The use of checkpoint-inhibitors has proven to be an advanced treatment method for various types of cancer around the world. In theRussian Federation, nivolumab has been successfully registered as a monotherapy for common or recurrent stomach or esophagogastric junction cancer after two or more lines of systemic antitumor drug therapy. This literature review focuses on the use of registered checkpoint inhibitors (nivolumab, pembrolizumab, ipilimumab) as mono- and/or combined therapy in tumors of the stomach and esophagogastric junction, including tumors with high microsat- ellite instability (MSI-high). This review includes a description of the main therapeutic approaches using checkpoint inhibitors: prescription in mono-mode, in combination with other checkpoint inhibitors (ipilimumab) and cytotoxic drugs, and in combination with tyrosine kinase inhibitors (regorafenib). Issues of efficiency and tolerability of these combinations in patients in different therapeutic lines are considered. The role of possible predictors of therapy response is analyzed: biomarkers such as PD-Ll, MSI, dMMR and TMB expression in tumor tissues as well as immunofenotyping in fresh biopsy samples are evaluated. This article reviews and evaluates the strengths and weaknesses of checkpoint inhibitors and their possible uses.

scholarly journals A new biological triangle in cancer: intestinal microbiota, immune checkpoint inhibitors and antibiotics

2021 ◽  
Author(s):  
Jie Zhang ◽  
Zhujiang Dai ◽  
Cheng Yan ◽  
Wenjie Zhang ◽  
Daorong Wang ◽  
...  
Keyword(s):  
Intestinal Microbiota ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Malignant Tumors ◽  
Checkpoint Inhibitors ◽  
Epidemiological Studies ◽  
Term Survival ◽  
Checkpoint Inhibitor Therapy ◽  
Rational Use Of Antibiotics

AbstractCancer immunotherapy has revolutionized the treatment of many malignant tumors. Although immune checkpoint inhibitors (ICIs) can reactivate the anti-tumor activity of immune cells, sensitivity to immune checkpoint inhibitor therapy depends on the complex tumor immune processes. In recent years, numerous researches have demonstrated the role of intestinal microbiota in immunity and metabolism of the tumor microenvironment, as well as the efficacy of immunotherapy. Epidemiological studies have further demonstrated the efficacy of antibiotic therapy on the probability of patients' response to ICIs and predictability of the short-term survival of cancer patients. Disturbance to the intestinal microbiota significantly affects ICIs-mediated immune reconstitution and is considered a possible mechanism underlying the development of adverse effects during antibiotic-based ICIs treatment. Intestinal microbiota, antibiotics, and ICIs have gradually become important considerations for the titer of immunotherapy. In the case of immunotherapy, the rational use of antibiotics and intestinal microbiota is expected to yield a better prognosis for patients with malignant tumors.

scholarly journals KLF2 Inhibits the Migration and Invasion of Prostate Cancer Cells by Downregulating MMP2

2018 ◽  
Vol 13 (1) ◽  
pp. 155798831881690 ◽  
Author(s):  
Binshuai Wang ◽  
Mingyuan Liu ◽  
Yimeng Song ◽  
Changying Li ◽  
Shudong Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Suppressor ◽  
Cell Function ◽  
Malignant Tumors ◽  
Suppressor Gene ◽  
Migration And Invasion ◽  
Tissue Samples ◽  
Tumor Tissues ◽  
Luciferase Activity Assay

KLF2, a member of the Kruppel-like factor (KLF) family, is thought to be a tumor suppressor in many kinds of malignant tumors. Its functions in prostate cancer (PCa) are unknown. This study aimed to explore the role of KLF2 in the migration and invasion of PCa cells. The expression of KLF2 was measured by immunohistochemistry in PCa tissues and in paired non-tumor tissues. KLF2 and MMP2 expression in cells was measured by Western blot and RT-qPCR. Adenoviruses and siRNAs were used in cell function tests to investigate the role of KLF2 in regulating MMP2. Interactions between KLF2 and MMP2 were analyzed by a luciferase activity assay. The present study, for the first time, identified that KLF2 was downregulated both in PCa clinical tissue samples and in cancer cell lines. The overexpression of KLF2 inhibited the migration and invasion of PCa cells via the suppression of MMP2.This study demonstrates that KLF2 might act as a tumor suppressor gene in PCa and that the pharmaceutical upregulation of KLF2 may be a potential approach for treatment.

scholarly journals Immunotherapy Strategies for Gastrointestinal Stromal Tumor

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3525
Author(s):  
Junaid Arshad ◽  
Philippos A. Costa ◽  
Priscila Barreto-Coelho ◽  
Brianna Nicole Valdes ◽  
Jonathan C. Trent
Keyword(s):  
Monoclonal Antibodies ◽  
Soft Tissue ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Locally Advanced ◽  
Soft Tissue Sarcomas ◽  
Standard Of Care ◽  
Current Standard ◽  
Molecular Alterations

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal soft tissue sarcoma of the gastrointestinal tract. The management of locally advanced or metastatic unresectable GIST involves detecting KIT, PDGFR, or other molecular alterations targeted by imatinib and other tyrosine kinase inhibitors. The role of immunotherapy in soft tissue sarcomas is growing fast due to multiple clinical and pre-clinical studies with no current standard of care. The potential therapies include cytokine-based therapy, immune checkpoint inhibitors, anti-KIT monoclonal antibodies, bi-specific monoclonal antibodies, and cell-based therapies. Here we provide a comprehensive review of the immunotherapeutic strategies for GIST.

Advancements in cancer chemotherapy

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Krzysztof Koper ◽  
Sławomir Wileński ◽  
Agnieszka Koper
Keyword(s):  
Hyperthermic Intraperitoneal Chemotherapy ◽  
Systemic Treatment ◽  
Malignant Tumors ◽  
Treatment Method ◽  
Anticancer Therapy ◽  
Cytostatic Drugs ◽  
Chemotherapy Administration ◽  
Modern Methods ◽  
Worse Prognosis

Abstract Chemotherapy is in most cases a method of systemic treatment of malignant tumors with cytostatic drugs. Although modern methods such as immunotherapy or targeted therapy are used more and more often nowadays, the role of chemotherapy in oncology is still significant. It can be used as an independent treatment method or in combination with other oncological therapies. The action of chemotherapy is closely linked to the cell cycle of the tumor. Advances in technology allow the introduction of different pharmaceutical forms of the same drug. Worse prognosis of metastatic tumors justifies the need to search for new, more effective treatment methods. The main problem of chemotherapy is the occurrence of adverse events. Reducing the frequency and severity of side effects is possible primarily by changing the technique of implementation of chemotherapy administration. These principles are fulfilled by new, increasingly popular therapeutic methods, such as: Perioperative Hyperthermic Intraperitoneal Chemotherapy (HIPEC), Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) or transarterial chemoembolization (TACE). The dynamic development of knowledge concerning cytostatic drugs, including targeting the tumor cell with the form of the drug, allows us to assume that in the future this direction will increase the effectiveness and safety of anticancer therapy.

scholarly journals BRCA1-Associated Protein 1 (BAP-1) as a Prognostic and Predictive Biomarker in Clear Cell Renal Cell Carcinoma: A Systematic Review

Kidney Cancer ◽  
2021 ◽  
pp. 1-13
Author(s):  
Shuchi Gulati ◽  
Melissa Previtera ◽  
Maria F. Czyzyk-Krzeska ◽  
Primo Nery Lara
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Clear Cell ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarker ◽  
Cell Renal Cell Carcinoma ◽  
Thymic Epithelial Tumors

BACKGROUND: The gene that encodes BRCA1-associated protein 1 (BAP1) has been reported to be dysregulated in several human cancers such as uveal melanoma, malignant pleural mesothelioma, hepatocellular carcinoma, thymic epithelial tumors, and clear-cell renal cell carcinoma (ccRCC). The gene is located on the human chromosome 3p21.3, encoding a deubiquitinase and acts as a classic two-hit tumor suppressor gene. BAP1 predominantly resides in the nucleus, where it interacts with several chromatin-associated factors, as well as regulates calcium signaling in the cytoplasm. As newer therapies continue to evolve for the management of RCC, it is important to understand the role of BAP1 mutation as a prognostic and predictive biomarker. OBJECTIVE: We aimed to systematically evaluate the role of BAP1 mutations in patients with RCC in terms of its impact on prognosis and its role as a predictive biomarker. METHODS: Following PRISMA guidelines, we performed a systematic literature search using PubMed and Embase through March 2021. Titles and abstracts were screened to identify articles for full-text and then a descriptive review was performed. RESULTS: A total of 490 articles were initially identified. Ultimately 71 articles that met our inclusion criteria published between 2012–2021 were included in the analysis. Data were extracted and organized to reflect the role of BAP1 alterations as a marker of prognosis as well as a marker of response to treatments, such as mTOR inhibitors, VEGF tyrosine kinase inhibitors, and immune checkpoint inhibitors. CONCLUSIONS: Alterations in BAP1 appear to be uniformly associated with poor prognosis in patients with RCC. Knowledge gaps remain with regard to the predictive relevance of BAP1 alterations, especially in the context of immunotherapy. Prospective studies are required to more precisely ascertain the predictive value of BAP1 alterations in RCC.

Expression, Regulation, and Role of an Oligopeptide Transporter: PEPT1 in Tumors

2021 ◽  
Vol 28 ◽  
Author(s):  
Xi Wang ◽  
Yiming Chen ◽  
Yongjuan Wang ◽  
Bangmao Wang ◽  
Jie Zhang ◽  
...  
Keyword(s):  
Malignant Tumor ◽  
Targeted Delivery ◽  
Intestinal Tract ◽  
Malignant Tumors ◽  
Critical Role ◽  
Expression Regulation ◽  
Antitumor Drugs ◽  
Molecular Biomarker ◽  
Tumor Tissues

: PEPT1 is a vital member of the proton-dependent oligopeptide transporters family (POTs). Many studies have confirmed that PEPT1 plays a critical role in the absorption of dipeptides, tripeptides, and pseudopeptides in the intestinal tract. In recent years, several studies have found that PEPT1 is highly expressed in malignant tumor tissues and cells. The abnormal expression of PEPT1 in tumors may be closely related to the progress of tumors, and hence, could be considered as a potential molecular biomarker for the diagnosis, treatment, and prognosis in malignant tumors. Furthermore, PEPT1 can be used as the delivery target to mediate the targeted delivery of antitumor drugs. Herein, the expression, regulation, and role of PEPT1 in tumors in recent years were reviewed.

scholarly journals Role of HDAC6 and Its Selective Inhibitors in Gastrointestinal Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Bingyi Zhou ◽  
Deliang Liu ◽  
Yuyong Tan
Keyword(s):  
Cardiovascular Diseases ◽  
Gastrointestinal Cancer ◽  
Histone Deacetylases ◽  
Digestive System ◽  
Malignant Tumors ◽  
Clinicopathological Characteristics ◽  
Cancer Occurrence ◽  
Tumor Tissues ◽  
Human Digestive System

Worldwide, cancer is the second leading cause of mortality after cardiovascular diseases. Among the numerous malignant tumors in human, digestive system cancers are the primary cause of morbidity and mortality. Acetylation and deacetylation are crucially involved in cancer occurrence and development; in addition, the deacetylation process is regulated by histone deacetylases (HDACs). Among the 18 human HDACs that have been reported, HDAC6 has been widely studied. There is upregulated HDAC6 expression in numerous types of tumor tissues and is closely associated with clinicopathological characteristics. Moreover, several HDAC6 inhibitors have been identified; furthermore, there has been extensive research on their ability to inhibit the growth of many tumors. This review summarizes the roles of HDAC6 in different primary digestive system malignancies.

The oncoprotein HBXIP – its functions and roles in oncogenesis

2018 ◽  
Vol 8 (2) ◽  
pp. 215-222
Author(s):  
M. Grudzinska ◽  
K. Lomperta ◽  
K. Jakubowska ◽  
P. Samocik ◽  
K. Jarząbek ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Treatment Effectiveness ◽  
Malignant Tumors ◽  
Interacting Protein ◽  
Complement Dependent Cytotoxicity ◽  
Tumor Tissues ◽  
A Cell ◽  
Cancerous Cells

Nowadays, Hepatitis B X interacting protein (HBXIP) is an object of scientists’ interest worldwide. It is a protein with significant involvement in the development of malignant tumors like breast or ovarian cancer. One of the most important functions of HBXIP is the regulation of cell proliferation, which is related to the progression of a cell cycle. Many studies provide the growing number of evidence that HBXIP plays various important roles, including the regulation of a cell cycle through complexes with survivin, belonging to the inhibitors of apoptosis and interactions with transcriptional factors like STAT4, SP1, TFIID or E2F1. It also has the influence on the promotion of tumor angiogenesis thanks to the association with VEGF and FGF8. Another important role of HBXIP is a reprogramming of glucose metabolism to conditions favorable to growing cancerous cells due to regulating the activation of SCO2 and PDHA1. Furthermore, it impacts on the complement-dependent cytotoxicity, also, HBXIP affects on lipid metabolism through disturbing of metabolic pathways of FAS. According to recent studies, HBXIP can be used as a prognostic biomarker in many tumors, including cervical cancer, ovarian cancer, and esophageal squamous cell carcinoma thanks to the high expression of this protein noted exclusively in these tumor tissues. What is even more interesting, it significantly correlates with clinical attributes like metastasis to lymph nodes or grading and in some cases can potentially be used as the indicator of prognosis of treatment effectiveness. The paper is review through main functions of HBXIP and its possible applications.

DDX39B Predicts Poor Survival and Associated with Clinical Benefit of Anti-PD-L1 Therapy in ccRCC

2021 ◽  
Vol 21 ◽  
Author(s):  
Jinhuan Wei ◽  
Jun Lu ◽  
Yun Cao ◽  
Gaosheng Yao ◽  
Yong Huang ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Clear Cell ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Therapy Response ◽  
Poor Survival ◽  
Cell Renal Cell Carcinoma ◽  
Fuhrman Grade

Background: Immune checkpoint inhibitors (ICI) have been shown to improve overall survival (OS) in clear cell renal cell carcinoma (ccRCC) patients. However, less than half of the ccRCC patients have objective response to ICI. Objective: We aim to assess the role of DDX39B in predicting ccRCC patients' OS and ICI therapy response. Methods: DDX39B was detected by immunohistochemistry in a tissue microarray of 305 ccRCC patients. DDX39B and its relationship with the prognosis of ccRCC were also evaluated in TCGA set and a RECA-EU set. The expression of DDX39B and patients survival was also analysed in two datasets of ccRCC patients treated with ICI. Results: Overexpression of DDX39B predicted poor OS of ccRCC patients in SYSU set, TCGA set, and a RECA-EU set. DDX39B expression was significantly positive with the expression of PD-L1 and other immunomodulators., DDX39B negatively correlated with cytotoxic T-lymphocyte and HDAC10 exon 3 inclusion in ccRCC. DDX39B knockdown decreased the expression of PD-L1 and increased the expression of HDAC10 exon 3 in renal cancer ACHN cells. Patients of ccRCC with lower levels of HDAC10 exon 3 inclusion have higher TNM stage, higher Fuhrman grade and poor OS. There was a tendency that patients with DDX39B high expression had longer OS and PFS than patients with DDX39B low expression in ccRCC patients treated with ICI. Conclusion: DDX39B gene is highly expressed in ccRCC and is closely related to patients’ OS. DDX39B might increase PD-L1 expression via the enhancement of HDAC10 exon 3 skipping, thereby promoting the ICI therapy response.

scholarly journals Nuclear PHGDH promotes neutrophil recruitment to drive liver cancer progression

2021 ◽  
Author(s):  
Hongwen Zhu ◽  
Hua Yu ◽  
Hu Zhou ◽  
Wencheng Zhu ◽  
Xiongjun Wang
Keyword(s):  
Liver Cancer ◽  
Cancer Progression ◽  
Malignant Tumors ◽  
Metabolic Dysregulation ◽  
Metabolic Role ◽  
Act Domain ◽  
Advanced Stages ◽  
Nuclear Location ◽  
Phosphoglycerate Dehydrogenase

Metabolic dysregulation and the communications between cancer and immune cells are emerging as two essential features of malignant tumors. In this study, we observed that nuclear localization of phosphoglycerate dehydrogenase (PHGDH) associates with poor prognosis of liver cancer patients, and Phgdh is required for liver cancer progression in a mouse model. Unexpectedly, the impairment of Phgdh enzyme activity exerts a slight effect on liver cancer model, indicating PHGDH contributes to liver cancer progression mainly depending on its non-metabolic roles with nuclear location. PHGDH uses its ACT domain to bind cMyc in nuclear and forms a transactivation axis PHGDH/p300/cMyc/AF9 which drives CXCL1/8 gene expression. Chemokines CXCL1/8 promotes neutrophils recruitment and then supports tumor associated macrophages (TAMs) filtration in liver, thereby urging liver cancer into advanced stages. Forced cytosolic location of PHGDH or destruction of the PHGDH/cMyc interaction abolishes the oncogenic function of nuclear PHGDH. Collectively, this study reveals a non-metabolic role of PHGDH with altered cellular location in liver cancer, and suggests a promising drug target for liver cancer therapy by targeting the interaction between PHGDH and undruggable cMyc.

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