Cherri Sara, Melocchi Laura, Gandolfi Laura, Rossi Giulio, Zaniboni Alberto
Department of Clinical Oncology, Fondazione Poliambulanza, 25124 Brescia, Italy.
Department of Anatomical Pathology, Fondazione Poliambulanza, 25124 Brescia, Italy.
Life (Basel). 2023 Jan 31;13(2):395. doi: 10.3390/life13020395.
In recent years, precision medicine has taken an increasing place in various branches of medical oncology, including colorectal cancer. Among the potentially relevant mutations for this cancer is the KRAS mutation, initially defined as "untargetable"; today, we see the birth of new molecules that target one of the variants of the KRAS mutation, KRAS G12C, having a significant impact on the therapeutic options for other malignancies, such as metastatic lung cancer. This fundamental step forward has stimulated scientific research on other potential targets of KRAS, both indirect and direct, and combination treatments aiming to overcome the mechanisms of resistance to these drugs that decrease in efficacy in colorectal cancer. What was once a negative predictive marker of response to anti-EGFR drugs today has become a potential target for targeted treatments. In turn, the prognostic role of the mutation has become extremely interesting, making it a potentially useful element in therapeutic decision-making, not only regarding oncological treatments but also in a more complex and complete manner within a global vision of the patient, involving other figures on the multidisciplinary team, such as surgeons, radiotherapists, and interventional radiologists.
近年来,精准医学在包括结直肠癌在内的肿瘤内科各分支领域中所占的地位日益重要。该癌症潜在的相关突变包括KRAS突变,最初它被定义为“不可靶向”;如今,我们看到了针对KRAS突变的一种变体KRAS G12C的新分子诞生,这对其他恶性肿瘤(如转移性肺癌)的治疗选择产生了重大影响。这一根本性的进展激发了对KRAS其他潜在靶点(包括间接和直接靶点)的科学研究,以及旨在克服这些药物在结直肠癌中疗效降低的耐药机制的联合治疗研究。曾经作为抗EGFR药物反应的阴性预测标志物,如今已成为靶向治疗的潜在靶点。反过来,该突变的预后作用也变得极具意义,使其成为治疗决策中一个潜在有用的因素,不仅涉及肿瘤治疗,而且在更全面的患者整体视野中,以更复杂和完整的方式,涉及多学科团队中的其他人员,如外科医生、放疗科医生和介入放射科医生。