scholarly journals Therapeutic Targeting of the Gas6/Axl Signaling Pathway in Cancer

2021 ◽  
Vol 22 (18) ◽  
pp. 9953
Author(s):  
Mai Tanaka ◽  
Dietmar W. Siemann
Keyword(s):  
Signaling Pathway ◽  
Receptor Tyrosine Kinase ◽  
Therapeutic Agents ◽  
Therapeutic Interventions ◽  
Therapeutic Resistance ◽  
Clinical Settings ◽  
Affinity Ligand ◽  
Current State ◽  
Cancer Types ◽  
High Affinity Ligand

Many signaling pathways are dysregulated in cancer cells and the host tumor microenvironment. Aberrant receptor tyrosine kinase (RTK) pathways promote cancer development, progression, and metastasis. Hence, numerous therapeutic interventions targeting RTKs have been actively pursued. Axl is an RTK that belongs to the Tyro3, Axl, MerTK (TAM) subfamily. Axl binds to a high affinity ligand growth arrest specific 6 (Gas6) that belongs to the vitamin K-dependent family of proteins. The Gas6/Axl signaling pathway has been implicated to promote progression, metastasis, immune evasion, and therapeutic resistance in many cancer types. Therapeutic agents targeting Gas6 and Axl have been developed, and promising results have been observed in both preclinical and clinical settings when such agents are used alone or in combination therapy. This review examines the current state of therapeutics targeting the Gas6/Axl pathway in cancer and discusses Gas6- and Axl-targeting agents that have been evaluated preclinically and clinically.

Advances of PD1 PD-L1 Signaling Pathway in Tumor Immunotherapy

2021 ◽  
Vol 7 (5) ◽  
pp. 1087-1096
Author(s):  
Yuchen Huo
Keyword(s):  
Signaling Pathway ◽  
Tumor Immunity ◽  
Patient Population ◽  
Tumor Immunotherapy ◽  
Therapeutic Agents ◽  
Cancer Types

L1 signaling pathway research in different cancer types. We will also discuss the limitations of antibody-based treatments and mechanisms related to PD-1/PD-L1 blockade resistance. In the end, we will also demonstrate potential solutions to overcome the challenges of current immunotherapy and the development of new therapeutic agents. Overall, immunotherapies targeting PD-1/PD-L1 pathway provide opportunities to boost anti-tumor immunity while there’s still problems waiting to be solved to allow larger patient population to be benefited.

Transcranial Electrical Stimulation in Post-Stroke Cognitive Rehabilitation

2016 ◽  
Vol 21 (1) ◽  
pp. 55-64 ◽  
Author(s):  
Silvia Convento ◽  
Cristina Russo ◽  
Luca Zigiotto ◽  
Nadia Bolognini
Keyword(s):  
Electrical Stimulation ◽  
Cognitive Rehabilitation ◽  
Cognitive Disorders ◽  
Spatial Neglect ◽  
Transcranial Electrical Stimulation ◽  
Clinical Settings ◽  
Post Stroke ◽  
Neuropsychological Disorders ◽  
Current State ◽  
Stimulation Technique

Abstract. Cognitive rehabilitation is an important area of neurological rehabilitation, which aims at the treatment of cognitive disorders due to acquired brain damage of different etiology, including stroke. Although the importance of cognitive rehabilitation for stroke survivors is well recognized, available cognitive treatments for neuropsychological disorders, such as spatial neglect, hemianopia, apraxia, and working memory, are overall still unsatisfactory. The growing body of evidence supporting the potential of the transcranial Electrical Stimulation (tES) as tool for interacting with neuroplasticity in the human brain, in turn for enhancing perceptual and cognitive functions, has obvious implications for the translation of this noninvasive brain stimulation technique into clinical settings, in particular for the development of tES as adjuvant tool for cognitive rehabilitation. The present review aims at presenting the current state of art concerning the use of tES for the improvement of post-stroke visual and cognitive deficits (except for aphasia and memory disorders), showing the therapeutic promises of this technique and offering some suggestions for the design of future clinical trials. Although this line of research is still in infancy, as compared to the progresses made in the last years in other neurorehabilitation domains, current findings appear very encouraging, supporting the development of tES for the treatment of post-stroke cognitive impairments.

scholarly journals Therapeutic Application of Monoclonal Antibodies in Pancreatic Cancer: Advances, Challenges and Future Opportunities

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1781
Author(s):  
Gustavo A. Arias-Pinilla ◽  
Helmout Modjtahedi
Keyword(s):  
Pancreatic Cancer ◽  
Monoclonal Antibodies ◽  
Antibody Therapy ◽  
Therapeutic Targets ◽  
Poor Response ◽  
Therapeutic Agents ◽  
Therapeutic Interventions ◽  
Western World ◽  
Wide Range ◽  
Novel Therapeutic

Pancreatic cancer remains as one of the most aggressive cancer types. In the absence of reliable biomarkers for its early detection and more effective therapeutic interventions, pancreatic cancer is projected to become the second leading cause of cancer death in the Western world in the next decade. Therefore, it is essential to discover novel therapeutic targets and to develop more effective and pancreatic cancer-specific therapeutic agents. To date, 45 monoclonal antibodies (mAbs) have been approved for the treatment of patients with a wide range of cancers; however, none has yet been approved for pancreatic cancer. In this comprehensive review, we discuss the FDA approved anticancer mAb-based drugs, the results of preclinical studies and clinical trials with mAbs in pancreatic cancer and the factors contributing to the poor response to antibody therapy (e.g. tumour heterogeneity, desmoplastic stroma). MAb technology is an excellent tool for studying the complex biology of pancreatic cancer, to discover novel therapeutic targets and to develop various forms of antibody-based therapeutic agents and companion diagnostic tests for the selection of patients who are more likely to benefit from such therapy. These should result in the approval and routine use of antibody-based agents for the treatment of pancreatic cancer patients in the future.

scholarly journals Dual Roles of the Activin Signaling Pathway in Pancreatic Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 821
Author(s):  
Wanglong Qiu ◽  
Chia-Yu Kuo ◽  
Yu Tian ◽  
Gloria H. Su
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathway ◽  
Critical Role ◽  
Genetic Mutations ◽  
Cancer Genetic ◽  
Dual Roles ◽  
Activin Signaling ◽  
Physiological Processes ◽  
Cancer Types ◽  
Related Proteins

Activin, a member of the TGF-β superfamily, is involved in many physiological processes, such as embryonic development and follicle development, as well as in multiple human diseases including cancer. Genetic mutations in the activin signaling pathway have been reported in many cancer types, indicating that activin signaling plays a critical role in tumorigenesis. Recent evidence reveals that activin signaling may function as a tumor-suppressor in tumor initiation, and a promoter in the later progression and metastasis of tumors. This article reviews many aspects of activin, including the signaling cascade of activin, activin-related proteins, and its role in tumorigenesis, particularly in pancreatic cancer development. The mechanisms regulating its dual roles in tumorigenesis remain to be elucidated. Further understanding of the activin signaling pathway may identify potential therapeutic targets for human cancers and other diseases.

scholarly journals Hypoxic tumor microenvironment: Implications for cancer therapy

2020 ◽  
Vol 245 (13) ◽  
pp. 1073-1086
Author(s):  
Sukanya Roy ◽  
Subhashree Kumaravel ◽  
Ankith Sharma ◽  
Camille L Duran ◽  
Kayla J Bayless ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Metabolic Regulation ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Tumor Vasculature ◽  
Therapeutic Strategies ◽  
Therapeutic Resistance ◽  
Low Oxygen ◽  
Cancer Types

Hypoxia or low oxygen concentration in tumor microenvironment has widespread effects ranging from altered angiogenesis and lymphangiogenesis, tumor metabolism, growth, and therapeutic resistance in different cancer types. A large number of these effects are mediated by the transcription factor hypoxia inducible factor 1⍺ (HIF-1⍺) which is activated by hypoxia. HIF1⍺ induces glycolytic genes and reduces mitochondrial respiration rate in hypoxic tumoral regions through modulation of various cells in tumor microenvironment like cancer-associated fibroblasts. Immune evasion driven by HIF-1⍺ further contributes to enhanced survival of cancer cells. By altering drug target expression, metabolic regulation, and oxygen consumption, hypoxia leads to enhanced growth and survival of cancer cells. Tumor cells in hypoxic conditions thus attain aggressive phenotypes and become resistant to chemo- and radio- therapies resulting in higher mortality. While a number of new therapeutic strategies have succeeded in targeting hypoxia, a significant improvement of these needs a more detailed understanding of the various effects and molecular mechanisms regulated by hypoxia and its effects on modulation of the tumor vasculature. This review focuses on the chief hypoxia-driven molecular mechanisms and their impact on therapeutic resistance in tumors that drive an aggressive phenotype. Impact statement Hypoxia contributes to tumor aggressiveness and promotes growth of many solid tumors that are often resistant to conventional therapies. In order to achieve successful therapeutic strategies targeting different cancer types, it is necessary to understand the molecular mechanisms and signaling pathways that are induced by hypoxia. Aberrant tumor vasculature and alterations in cellular metabolism and drug resistance due to hypoxia further confound this problem. This review focuses on the implications of hypoxia in an inflammatory TME and its impact on the signaling and metabolic pathways regulating growth and progression of cancer, along with changes in lymphangiogenic and angiogenic mechanisms. Finally, the overarching role of hypoxia in mediating therapeutic resistance in cancers is discussed.

A review of current and future medical therapies for cerebral vasospasm following aneurysmal subarachnoid hemorrhage

2006 ◽  
Vol 21 (3) ◽  
pp. 1-7 ◽  
Author(s):  
J Mocco ◽  
Brad E. Zacharia ◽  
Ricardo J. Komotar ◽  
E. Sander Connolly
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Relevant Literature ◽  
Therapeutic Interventions ◽  
Common Complication ◽  
Current State ◽  
Threefold Increase ◽  
Poor Understanding ◽  
Medical Therapies

✓In an effort to help clarify the current state of medical therapy for cerebral vasospasm, the authors reviewed the relevant literature on the established medical therapies used for cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH), and they discuss burgeoning areas of investigation. Despite advances in the treatment of aneurysmal SAH, cerebral vasospasm remains a common complication and has been correlated with a 1.5- to threefold increase in death during the first 2 weeks after hemorrhage. A number of medical, pharmacological, and surgical therapies are currently in use or being investigated in an attempt to reverse cerebral vasospasm, but only a few have proven to be useful. Although much has been elucidated regarding its pathophysiology, the treatment of cerebral vasospasm remains a dilemma. Although a poor understanding of SAH-induced cerebral vasospasm pathophysiology has, to date, hampered the development of therapeutic interventions, current research efforts promise the eventual production of new medical therapies.

Sign in / Sign up

Export Citation Format

Share Document