PDF(Pubmed)
Abstract：
Multiple myeloma remains an incurable disease despite numerous novel agents being approved in the last decade. Furthermore, disease behavior and susceptibility to current treatments often vary drastically from patient to patient. To date there are no approved therapies in myeloma that are targeted to specific patient populations based on genomic or immunologic findings. Precision medicine, using biomarkers descriptive of a specific tumor\'s biology and predictive of response to appropriate agents, may continue to push the field forward by expanding our treatment arsenal while refining our ability to expose patients to only those treatments likely to be efficacious. Extensive research efforts have been carried out in this endeavor including the use of agents targeting Bcl2 and the RAS/MAPK and PI3K/AKT/mTOR pathways. Thus far, clinical trials have yielded occasional successes intermixed with disappointments, reflecting significant hurdles which still remain including the complex crosstalk between oncogenic pathways and the nonlinear genetic development of myeloma, prone to cultivating sub-clones with distinctive mutations. In this review, we explore the landscape of precision therapeutics in multiple myeloma and underscore the degree to which research efforts have produced tangible clinical results.
摘要：
尽管在过去十年中批准了许多新型药物，但多发性骨髓瘤仍然是一种无法治愈的疾病。此外，疾病行为和对当前治疗的敏感性通常因患者而异。迄今为止，尚无基于基因组或免疫学发现的针对特定患者群体的骨髓瘤的批准疗法。精准医学,使用描述特定肿瘤生物学的生物标志物，并预测对适当药物的反应，通过扩大我们的治疗库，同时提高我们仅将患者暴露于可能有效的治疗方法的能力，可以继续推动该领域的发展。在这一努力中已经进行了广泛的研究努力,包括使用靶向Bcl2和RAS/MAPK和PI3K/AKT/mTOR途径的试剂。到目前为止,临床试验偶尔取得成功，但令人失望，反映了仍然存在的重大障碍，包括致癌途径和骨髓瘤的非线性遗传发育之间的复杂串扰，容易培养具有独特突变的亚克隆。在这次审查中,我们探索了多发性骨髓瘤精准治疗的前景，并强调了研究工作取得切实临床成果的程度。
