Oncology Department, Geneva University Hospital, 1205 Geneva, Switzerland.
Genolier Cancer Center, 1272 Genolier, Switzerland.
Curr Oncol. 2023 Apr 30;30(5):4648-4662. doi: 10.3390/curroncol30050351.
GIST (gastrointestinal stromal tumors) represent 20% of sarcomatous tumors and 1-2% of primary gastrointestinal cancers. They have an excellent prognosis when localized and resectable, though their prognosis is poor in the metastatic setting, with limited options after the second line until recently. Four lines are now standard in KIT-mutated GIST and one in PDGFRA-mutated GIST. An exponential growth of new treatments is expected in this era of molecular diagnostic techniques and systematic sequencing. Currently, the main challenge remains the emergence of resistance linked to secondary mutations caused by selective pressure induced by TKIs. Repeating biopsies to tailor treatments might be a step in the right direction, and liquid biopsies at progression may offer a non-invasive alternative. New molecules with wider KIT inhibition are under investigation and could change the catalog and the sequence of existing treatments. Combination therapies may also be an approach to overcome current resistance mechanisms. Here, we review the current epidemiology and biology of GIST and discuss future management options, with an emphasis on genome-oriented therapies.
GIST(胃肠道间质瘤)占肉瘤肿瘤的 20%,占原发性胃肠道癌症的 1-2%。当局限且可切除时,其预后良好,而在转移环境下预后较差,二线治疗后选择有限,直到最近才有了新的选择。目前,在分子诊断技术和系统测序的时代,预计会有越来越多的新治疗方法出现。目前,主要的挑战仍然是由于 TKI 诱导的选择压力引起的继发突变导致的耐药性的出现。重复活检以调整治疗可能是正确方向上的一步,而进展时的液体活检可能提供一种非侵入性的替代方法。具有更广泛 KIT 抑制作用的新型分子正在研究中,可能会改变现有的治疗方法的目录和顺序。联合疗法也可能是克服当前耐药机制的一种方法。在这里,我们回顾了 GIST 的当前流行病学和生物学,并讨论了未来的管理选择,重点是基于基因组的治疗。