靶向疗法的出现导致了治疗选择及其在肿瘤学领域的结果的巨大改善。然而,许多癌症通过开发中靶或脱靶耐药机制胜过精准药物。获得抵抗治疗的能力是肿瘤的规则而不是例外,在大多数癌症患者中实现持久缓解仍然是一个主要的医疗保健挑战。这里,我们讨论了新兴的策略,这些策略利用创新的高通量筛查技术,在接受治疗的癌症患者中出现靶点和脱靶的耐药机制之前对其进行预测.我们将这些方法分为非系统方法,如随机诱变或长期药物治疗,和系统的方法,依靠成簇的规则间隔短回文重复(CRISPR)系统,饱和诱变,或计算方法。所有这些新的发展,特别是基于全基因组CRISPR的筛选平台,大大加快了确定癌症耐药机制的过程,并为未来的治疗开辟了新的途径。
The advent of targeted therapies has led to tremendous improvements in treatment options and their outcomes in the field of oncology. Yet, many cancers outsmart precision drugs by developing on-target or off-target resistance mechanisms. Gaining the ability to resist treatment is the rule rather than the exception in tumors, and it remains a major healthcare challenge to achieve long-lasting remission in most cancer patients. Here, we discuss emerging strategies that take advantage of innovative high-throughput screening technologies to anticipate on- and off-target resistance mechanisms before they occur in treated cancer patients. We divide the methods into non-systematic approaches, such as random mutagenesis or long-term drug treatment, and systematic approaches, relying on the clustered regularly interspaced short palindromic repeats (CRISPR) system, saturated mutagenesis, or computational methods. All these new developments, especially genome-wide CRISPR-based screening platforms, have significantly accelerated the processes for identification of the mechanisms responsible for cancer drug resistance and opened up new avenues for future treatments.