Expert Opinion on Therapeutic Targets最新文献

Introduction: Cancer immunotherapy has revolutionized the field of oncology, offering new hope to patients with advanced malignancies. Tumor-induced immunosuppression limits the effectiveness of current immunotherapeutic strategies, such as PD-1/PDL-1 checkpoint inhibitors. Adenosine, a purine nucleoside molecule, is crucial to this immunosuppression because it stops T cells from activating and helps regulatory T cells grow. Targeting the adenosine pathway and blocking PD-1/PDL-1 is a potential way to boost the immune system's response to tumors.

Areas covered: This review discusses the current understanding of the adenosine pathway in tumor immunology and the preclinical and clinical data supporting the combination of adenosine pathway inhibitors with PD-1/PDL-1 blockade. We also discuss the challenges and future directions for developing combination immunotherapy targeting the adenosine pathway and the PD-1/PDL-1 axis for cancer treatment.

Expert opinion: The fact that the adenosine signaling pathway controls many immune system processes suggests that it has a wide range of therapeutic uses. Within the next five years, there will be tremendous progress in this area, and the standard of care for treating malignant tumors will have switched from point-to-point therapy to the integration of immunological networks comprised of multiple signaling pathways, like the adenosine axis.

Introduction: Inhibition of the enzymatic function of HDAC6 is currently being explored in clinical trials ranging from peripheral neuropathies to cancers. Advances in selective HDAC6 inhibitor discovery allowed studying highly efficacious brain penetrant and peripheral restrictive compounds for treating PNS and CNS indications.

Areas covered: This review explores the multifactorial role of HDAC6 in cells, the common pathological hallmarks of PNS and CNS disorders, and how HDAC6 modulates these mechanisms. Pharmacological inhibition of HDAC6 and genetic knockout/knockdown studies as a therapeutic strategy in PNS and CNS indications were analyzed. Furthermore, we describe the recent developments in HDAC6 PET tracers and their utility in CNS indications. Finally, we explore the advancements and challenges with HDAC6 inhibitor compounds, such as hydroxamic acid, fluoromethyl oxadiazoles, HDAC6 degraders, and thiol-based inhibitors.

Expert opinion: Based on extensive preclinical evidence, pharmacological inhibition of HDAC6 is a promising approach for treating both PNS and CNS disorders, given its involvement in neurodegeneration and aging-related cellular processes. Despite the progress in the development of selective HDAC6 inhibitors, safety concerns remain regarding their chronic administration in PNS and CNS indications, and the development of novel compound classes and modalities inhibiting HDAC6 function offer a way to mitigate some of these safety concerns.

Introduction: Acute graft-versus-host disease (aGVHD) is a major complication of post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) that severely impacts patient survival and quality of life. Despite advancements in standard care, therapeutic outcomes remain suboptimal, necessitating the exploration of innovative strategies.

Areas covered: This review synthesizes preclinical research focusing on novel therapeutic targets and strategies that may enhance treatment efficacy. We critically analyzed the role of specific T-cell subsets, cytokine modulators, and intracellular signaling pathways in reducing aGVHD severity. Emphasis is placed on experimental findings that illuminate the mechanisms of immune tolerance and survival improvement. We discuss the translation of these findings into potential clinical trials and evaluate the challenges and progress in implementing these strategies, including scalability and impact on the graft-versus-leukemia (GVL) effect.

Expert opinion: Our review summarizes the latest therapeutic targets and strategies in preclinical research for aGVHD, aiming to bridge the gap between clinical and experimental medicine. By integrating immunology, genetics, and cytology, we seek to enhance the translation of preclinical findings into clinical strategies. This multidisciplinary approach is expected to improve patient outcomes in aGVHD treatment, ultimately leading to more effective and safer therapies.

Introduction: This review highlights the critical role of the endocannabinoid system (ECS) in regulating neuropathic pain and explores the therapeutic potential of cannabinoids. Understanding the mechanisms of the ECS, including its receptors, endogenous ligands, and enzymatic routes, can lead to innovative treatments for chronic pain, offering more effective therapies for neuropathic conditions. This review bridges the gap between preclinical studies and clinical applications by emphasizing ECS modulation for better pain management outcomes.

Areas covered: A review mapped the existing literature on neuropathic pain and the effects of modulating the ECS using natural and synthetic cannabinoids. This analysis examined ECS components and their alterations in neuropathic pain, highlighting the peripheral, spinal, and supraspinal mechanisms. This review aimed to provide a thorough understanding of the therapeutic potential of cannabinoids in the management of neuropathic pain.

Expert opinion: Advances in cannabinoid research have shown significant potential for the management of chronic neuropathic pain. The study emphasizes the need for high-quality clinical trials and collaborative efforts among researchers, clinicians, and regulatory bodies to ensure safe and effective integration of cannabinoids into pain management protocols. Understanding the mechanisms and optimizing cannabinoid formulations and delivery methods are crucial for enhancing therapeutic outcomes.

Introduction: The bone marrow microenvironment (BME) is critical for healthy hematopoiesis and is often disrupted in hematologic malignancies. Tumor-associated macrophages (TAMs) are a major cell type in the tumor microenvironment (TME) and play a significant role in tumor growth and progression. Targeting TAMs and modulating their polarization is a promising strategy for cancer therapy.

Areas covered: In this review, we discuss the importance of TME and different multiple possible targets to modulate immunosuppressive TAMs such as: CD123, Sphingosine 1-Phosphate Receptors, CD19/CD1d, CCR4/CCL22, CSF1R (CD115), CD24, CD40, B7 family proteins, MARCO, CD47, CD163, CD204, CD206 and folate receptors.

Expert opinion: Innovative approaches to combat the immunosuppressive milieu of the tumor microenvironment in hematologic malignancies are of high clinical significance and may lead to increased survival, improved quality of life, and decreased toxicity of cancer therapies. Standard procedures will likely involve a combination of CAR T/NK-cell therapies with other treatments, leading to more comprehensive cancer care.

Introduction: Psoriasis is a chronic immune-mediated disorder affecting over 2-3% of the population worldwide, significantly impacting quality of life. Despite the availability of various therapeutic interventions, concerns persist regarding lesion recurrence and potential alterations in immune surveillance promoting cancer progression. Recent advancements in understanding cellular and molecular pathways have unveiled key factors in psoriasis etiology, including IL-17, 22, 23, TNF-α, PDE-4, JAK-STAT inhibitors, and AhR agonists. This work explores the potential of S-phase kinase-associated protein 2 (Skp2) as a therapeutic target in psoriasis.

Area covered: This review covers the current understanding of psoriasis pathophysiology, including immune dysregulation, and the role of keratinocytes and ubiquitin. It also delves into Skp2 role in cell cycle regulation, and its correlation with angiogenesis and ubiquitin in psoriasis. The evolving therapeutic approaches targeting Skp2, including small molecule inhibitors, are also discussed.

Expert opinion: Targeting Skp2 holds promise for developing novel therapeutic approaches for psoriasis. By modulating Skp2 activity or expression, it may be possible to intervene in inflammatory and proliferative processes underlying the disease. Further research into Skp2 inhibitors and their efficacy in preclinical and clinical settings is warranted to harness the full potential of Skp2 as a therapeutic target in psoriasis management.

Introduction: Uterine fibroids, the most common nonmalignant tumors affecting the female genital tract, are a significant medical challenge. This article focuses on the most recent studies that attempted to identify novel non-hormonal therapeutic targets and strategies in UF therapy.

Areas covered: This review covers the analysis of the pharmacological and biological mechanisms of the action of natural substances and the role of the microbiome in reference to UFs. This study aimed to determine the potential role of these compounds in UF prevention and therapy.

Expert opinion: While there are numerous approaches for treating UFs, available drug therapies for disease control have not been optimized yet. This review highlights the biological potential of vitamin D, EGCG and other natural compounds, as well as the microbiome, as promising alternatives in UF management and prevention. Although these substances have been quite well analyzed in this area, we still recommend conducting further studies, particularly randomized ones, in the field of therapy with these compounds or probiotics. Alternatively, as the quality of data continues to improve, we propose the consideration of their integration into clinical practice, in alignment with the patient's preferences and consent.