Expert Opinion on Therapeutic Targets最新文献

Introduction: Cyclin-dependent kinase 7 (CDK7) is a key regulator of transcription and the cell cycle, with its dysregulation linked to tumorigenesis and chemoresistance. CDK7 serves as an unfavorable prognostic marker in multiple cancers and is significantly overexpressed in patients with poor prognosis, including those with lung and pancreatic cancer.

Areas covered: This review explores the role of CDK7 in tumorigenesis, focusing on transcriptional regulation, tumor metabolism, and therapy resistance. The development of CDK7 inhibitors has gained attention as a potential strategy to overcome chemoresistance. Notably, cancer cells exhibit sensitivity to CDK7 inhibitors at doses well tolerated by normal cells, supporting their clinical applicability. This review examines key CDK7 inhibitors, including THZ1, LDC4297, and YKL-5-124, in non-small-cell lung cancer (NSCLC), small-cell lung cancer (SCLC), and pancreatic ductal adenocarcinoma (PDAC), highlighting their mechanisms and therapeutic potential. Resistance mechanisms and combination strategies with chemotherapy, targeted therapies, or immunotherapy are also discussed.

Expert opinion: Despite promising preclinical results, challenges remain, including specificity, biomarker identification, and clinical validation. Further research is needed to optimize dosing, address resistance, and translate CDK7 inhibitors into clinical practice. Lastly, ongoing and future clinical trials will be essential to determining their therapeutic potential in PDAC, NSCLC, and SCLC.

Introduction: With the increasing prevalence of aging populations, the incidence of neurodegenerative diseases continues to rise, posing a serious threat to human health and quality of life. Owing to the highly complex pathogenesis of these disorders, the identification of effective therapeutic targets remains a major challenge. CD44, a cell surface glycoprotein, plays a central role in regulating cell proliferation, survival, adhesion, and migration. Emerging evidence further indicates that CD44 contributes to NF-κB activation, thereby amplifying inflammatory responses.

Areas covered: Given its central role in neuroinflammation, CD44 has attracted increasing attention as a potential therapeutic target for neurodegenerative diseases. This review explores the involvement of CD44 in amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), and Parkinson's disease (PD), with particular emphasis on its contributions to neuroinflammatory processes, neuronal survival, and pathological protein aggregation.

Expert opinion: Chronic low-grade neuroinflammation is a major driver of neurodegenerative diseases, including ALS, AD, and PD. Growing evidence implicates CD44 as a key contributor to disease pathogenesis, with several studies reporting significantly elevated CD44 expression in affected patients. These findings highlight the role of CD44 in disease progression and suggest that targeting CD44-mediated inflammation may offer a promising therapeutic strategy for neurodegenerative disorders.

Introduction: Attention-deficit/hyperactivity disorder (ADHD) is a common neuropsychiatric disorder of inattention, hyperactivity, and impulsivity. Roles for dopamine and norepinephrine are widely recognized; however, the role of serotonergic neurotransmission is less clear. This systematic literature review aimed to determine if changes in serotonin transmission are implicated in the neurobiology of ADHD.

Methods: A search of published literature was conducted. Eligible publications addressing the role of serotonin, its receptor family, and/or its transporter in the neurobiology of ADHD were selected according to prespecified criteria. The quality of evidence was graded.

Results: Of 95 publications meeting our criteria, many (n = 60) were nonclinical studies. Most publications were rated as containing medium- (62.1%) or high-grade (17.9%) evidence. Multiple strands of evidence were found to implicate serotonin in ADHD, with 81.1% of the identified articles providing support for altered levels of serotonin production, binding, transport, or degradation in ADHD.

Conclusions: Substantial evidence implicates serotonin in the neurobiology of ADHD and in the regulation of the catecholaminergic systems believed to be dysregulated by the disorder. Yet this evidence is incomplete and, at times, conflicting. It does suggest, however, that medications that engage the serotonin system should be tested for their efficacy in the treatment of ADHD.