Archives of pharmacology and therapeutics最新文献

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Targeted Therapy in Non-Muscle Invasive Bladder Cancer-Clinical Updates. 非肌肉浸润性膀胱癌的靶向治疗

Archives of pharmacology and therapeutics

Pub Date : 2024-01-01 DOI: 10.33696/pharmacol.6.056

Rachel Passarelli, John Pfail, David Golombos, Thomas L Jang, Vignesh T Packiam, Saum Ghodoussipour

Non muscle invasive bladder cancer (NMIBC) comprises almost 75% of all bladder cancer (BC) diagnoses. Longstanding intravesical treatment options include chemotherapy or Bacillus Calmette-Guerin (BCG). However, despite these treatment options, there is a high rate of relapse for NMIBC patients, reaching up to 40-50% for patients with high risk disease. Radical cystectomy is recommended by guideline committees for patients with high risk NMIBC and for patients who fail intravesical treatment options however this is a procedure with high morbidity and many patients are not good candidates or prefer more conservative treatment approaches. Given this and the high failure rates of current therapies, much ongoing research in NMIBC is focused on other bladder sparing treatment modalities. There have been new advances in molecular features of BC with findings of genetic alterations in NMIBC leading way to a rise in precision medicine targeting a patient's individual gene mutation. While data surrounding these targeted therapies in NMIBC specifically are all preliminary, many trials are currently underway derived from success in targeted treatments for locally advanced or metastatic BC. Preliminary results are promising and the targeted therapies for NMIBC are increasing. We performed a PubMed and Medline (OVID) literature review assessing recently published studies on targeted therapy on NMIBC, and an additional search on clinicaltrials.gov for active clinical trials. We report on preliminary outcomes and ongoing later stage trials for targeted therapies in NMIBC and anticipate upcoming promising changes to the treatment landscape.

非肌肉浸润性膀胱癌（NMIBC）占所有膀胱癌（BC）诊断的近75%。长期的膀胱内治疗方案包括化疗或卡介苗。然而，尽管有这些治疗选择，NMIBC患者的复发率很高，高危患者复发率高达40-50%。指南委员会推荐根治性膀胱切除术用于高风险NMIBC患者和膀胱内治疗失败的患者，但这是一种高发病率的手术，许多患者不是很好的候选人或更喜欢保守的治疗方法。考虑到这一点以及目前治疗方法的高失败率，许多正在进行的NMIBC研究都集中在其他膀胱保留治疗方式上。随着NMIBC基因改变的发现，在BC的分子特征方面取得了新的进展，这导致了针对患者个体基因突变的精准医学的兴起。虽然这些靶向治疗NMIBC的数据都是初步的，但目前正在进行的许多试验都是基于局部晚期或转移性BC靶向治疗的成功。初步结果是有希望的，针对NMIBC的靶向治疗正在增加。我们进行了PubMed和Medline （OVID）的文献综述，评估了最近发表的针对NMIBC的靶向治疗研究，并在clinicaltrials.gov上进行了额外的搜索，以寻找正在进行的临床试验。我们报告了NMIBC靶向治疗的初步结果和正在进行的后期试验，并预测了治疗前景即将发生的有希望的变化。

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引用次数: 0

Why Can Modulation of α6-Containing GABA_A Receptors Reduce the Symptoms of Multiple Neuropsychiatric Disorders? 为什么调节含 α6 的 GABAA 受体能减轻多种神经精神疾病的症状？

Archives of pharmacology and therapeutics

Pub Date : 2024-01-01 DOI: 10.33696/Pharmacol.6.047

Werner Sieghart

α6-containing GABA_A receptors (α6GABA_ARs) are strongly expressed in cerebellar granule cells, where they mediate a correctly timed and precise coordination of all muscle groups that execute behavior and protect the brain from information overflow. Recently, it was demonstrated that positive modulators with a high selectivity for α6GABA_ARs (α6-modulators) can reduce the symptoms of multiple neuropsychiatric disorders in respective animal models to an extent comparable with established clinical therapeutics. Here, these incredible findings are discussed and explained. So far, the beneficial actions of α6-modulators and their lack of side effects have only been demonstrated in animal models of the respective disorders. Preclinical studies have demonstrated their suitability for further drug development. Future human studies have to investigate their safety and possible side effects, and to clarify to which extent individual symptoms of the respective disorders can be reduced by α6-modulators in patients during acute and chronic dosing. Due to their broad therapeutic potential, α6-modulators might become a valuable new treatment option for multiple neuropsychiatric disorders.

含α6的GABAA受体（α6GABAARs）在小脑颗粒细胞中强烈表达，它们在小脑颗粒细胞中介导所有执行行为的肌肉群的正确定时和精确协调，并保护大脑免受信息溢出的影响。最近的研究表明，对α6GABAARs具有高度选择性的正性调节剂（α6-调节剂）可以在相应的动物模型中减轻多种神经精神疾病的症状，其程度可媲美现有的临床疗法。本文将对这些令人难以置信的发现进行讨论和解释。迄今为止，α6-调节剂的有益作用及其无副作用仅在相关疾病的动物模型中得到证实。临床前研究已证明它们适合进一步的药物开发。未来的人体研究必须对其安全性和可能的副作用进行调查，并明确α6-调节剂在急性和慢性用药期间能在多大程度上减轻患者的各种疾病症状。由于α6-调节剂具有广泛的治疗潜力，因此可能成为治疗多种神经精神疾病的一种有价值的新选择。

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