scholarly journals Targeting KRAS in Lung Cancer Beyond KRAS G12C Inhibitors: The Immune Regulatory Role of KRAS and Novel Therapeutic Strategies

2022 ◽  
Vol 11 ◽  
Author(s):  
Marc Cucurull ◽  
Lucia Notario ◽  
Montse Sanchez-Cespedes ◽  
Cinta Hierro ◽  
Anna Estival ◽  
...  
Keyword(s):  
Tumor Heterogeneity ◽  
Regulatory Role ◽  
Lung Cancers ◽  
Downstream Signaling ◽  
Tumor Immune Microenvironment ◽  
Covalent Inhibitors ◽  
Early Phase Clinical Trials ◽  
Novel Therapeutic Strategies ◽  
Lung Adenocarcinomas

Approximately 20% of lung adenocarcinomas harbor KRAS mutations, an oncogene that drives tumorigenesis and has the ability to alter the immune system and the tumor immune microenvironment. While KRAS was considered “undruggable” for decades, specific KRAS G12C covalent inhibitors have recently emerged, although their promising results are limited to a subset of patients. Several other drugs targeting KRAS activation and downstream signaling pathways are currently under investigation in early-phase clinical trials. In addition, KRAS mutations can co-exist with other mutations in significant genes in cancer (e.g., STK11 and KEAP1) which induces tumor heterogeneity and promotes different responses to therapies. This review describes the molecular characterization of KRAS mutant lung cancers from a biologic perspective to its clinical implications. We aim to summarize the tumor heterogeneity of KRAS mutant lung cancers and its immune-regulatory role, to report the efficacy achieved with current immunotherapies, and to overview the therapeutic approaches targeting KRAS mutations besides KRAS G12C inhibitors.

scholarly journals Tumor-Associated Macrophages: Critical Players in Drug Resistance of Breast Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Maoyu Xiao ◽  
Jun He ◽  
Liyang Yin ◽  
Xiguan Chen ◽  
Xuyu Zu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Therapeutic Strategies ◽  
Tumor Associated Macrophages ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment ◽  
Potential Possibility ◽  
Underlying Mechanisms ◽  
Novel Therapeutic Strategies

Drug resistance is one of the most critical challenges in breast cancer (BC) treatment. The occurrence and development of drug resistance are closely related to the tumor immune microenvironment (TIME). Tumor-associated macrophages (TAMs), the most important immune cells in TIME, are essential for drug resistance in BC treatment. In this article, we summarize the effects of TAMs on the resistance of various drugs in endocrine therapy, chemotherapy, targeted therapy, and immunotherapy, and their underlying mechanisms. Based on the current overview of the key role of TAMs in drug resistance, we discuss the potential possibility for targeting TAMs to reduce drug resistance in BC treatment, By inhibiting the recruitment of TAMs, depleting the number of TAMs, regulating the polarization of TAMs and enhancing the phagocytosis of TAMs. Evidences in our review support it is important to develop novel therapeutic strategies to target TAMs in BC to overcome the treatment of resistance.

scholarly journals The Emerging Role of BDNF/TrkB Signaling in Cardiovascular Diseases

Life ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 70
Author(s):  
Peng-Zhou Hang ◽  
Hua Zhu ◽  
Pei-Feng Li ◽  
Jie Liu ◽  
Feng-Qin Ge ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Metabolic Diseases ◽  
Current Evidence ◽  
Downstream Signaling ◽  
Diagnosis And Prognosis ◽  
Potential Biomarker ◽  
The Central Nervous System ◽  
Artery Disease ◽  
Novel Therapeutic Strategies

Brain-derived neurotrophic factor (BDNF) is one of the most abundant neurotrophins in the central nervous system. Numerous studies suggest that BDNF has extensive roles by binding to its specific receptor, tropomyosin-related kinase receptor B (TrkB), and thereby triggering downstream signaling pathways. Recently, growing evidence highlights that the BDNF/TrkB pathway is expressed in the cardiovascular system and closely associated with the development and outcome of cardiovascular diseases (CVD), including coronary artery disease, heart failure, cardiomyopathy, hypertension, and metabolic diseases. Furthermore, circulating BDNF has also been revealed as a new potential biomarker for both diagnosis and prognosis of CVD. In this review, we discuss the current evidence of the emerging role of BDNF/TrkB signaling and address the challenges that remain in translating these discoveries to novel therapeutic strategies for CVD.

scholarly journals Multiscale Agent-Based and Hybrid Modeling of the Tumor Immune Microenvironment

Processes ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 37 ◽  
Author(s):  
Kerri-Ann Norton ◽  
Chang Gong ◽  
Samira Jamalian ◽  
Aleksander Popel
Keyword(s):  
Immune Response ◽  
Tumor Heterogeneity ◽  
Computational Models ◽  
Digital Pathology ◽  
Hybrid Modeling ◽  
Immune Microenvironment ◽  
Agent Based ◽  
Tumor Immune Microenvironment ◽  
Cancer Tumor

Multiscale systems biology and systems pharmacology are powerful methodologies that are playing increasingly important roles in understanding the fundamental mechanisms of biological phenomena and in clinical applications. In this review, we summarize the state of the art in the applications of agent-based models (ABM) and hybrid modeling to the tumor immune microenvironment and cancer immune response, including immunotherapy. Heterogeneity is a hallmark of cancer; tumor heterogeneity at the molecular, cellular, and tissue scales is a major determinant of metastasis, drug resistance, and low response rate to molecular targeted therapies and immunotherapies. Agent-based modeling is an effective methodology to obtain and understand quantitative characteristics of these processes and to propose clinical solutions aimed at overcoming the current obstacles in cancer treatment. We review models focusing on intra-tumor heterogeneity, particularly on interactions between cancer cells and stromal cells, including immune cells, the role of tumor-associated vasculature in the immune response, immune-related tumor mechanobiology, and cancer immunotherapy. We discuss the role of digital pathology in parameterizing and validating spatial computational models and potential applications to therapeutics.

Regulatory role of resistin on ovarian function

2014 ◽  
Author(s):  
Agnieszka Rak-Mardyla ◽  
Anna Wrobel ◽  
Eliza Drwal ◽  
Ewa Gregoraszczuk
Keyword(s):  
Ovarian Function ◽  
Regulatory Role

The tyrosine kinase TEK is differentially expressed in non-small cell lung adenocarcinomas.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
United States ◽  
Tyrosine Kinase ◽  
Lung Adenocarcinoma ◽  
Microarray Data ◽  
The United States ◽  
Small Cell ◽  
Small Cell Lung ◽  
Significant Differential Expression ◽  
Lung Cancers ◽  
Lung Adenocarcinomas

Non-small cell lung adenocarcinoma (NSCLC) is a leading cause of death in the United States and worldwide (1, 2). We mined published microarray data (3, 4, 5) to discover genes associated with NSCLC. We identified significant differential expression of the tyrosine kinase TEK in tumors from patients with NSCLC. TEK may be of relevance to the initiation, progression or maintenance of non-small cell lung cancers.

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