Lung cancer, platinum analog-based frontline treatment and pharmacogenetic limitations.

Maryam Saqib, Zari Salahud Din, Sehrish Zafar, Nayla Munawar, Rukhsana Nawaz, Sagheer Ahmed, Mohammad Hamid Hamdard
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Abstract

Lung cancer has the highest mortality rate among all the highly prevalent neoplasia globally. The major concern with its frontline treatment-cisplatin, is the rapid progression of chemoresistance and multi-organ-based toxicities including hearing loss and tinnitus, nephrotoxicity, hepatotoxicity and myelosuppression including anemia and neutropenia. In this review, studies concluding the association of single nucleotide polymorphisms (SNP) in disparate genes with aforementioned toxicity points are summarized to observe the pharmacogenomic pattern. Especially, SNPs in ATP7B, ERCC-1, ERCC-2, MATE-1, OCT-2, ABCB-1, ABCC-1, ABCG-2, ABCC-2, SLC22A, ERCC-5, BRCA-1, GSTM-3, GSTM-4 and GSTM-5 genes appear to be associated with the therapeutic response and/or adverse effects of cisplatin. We recommend utilizing this information to minimize the risk of treatment failure due to chemoresistance and adverse effects on other organs.

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肺癌、以铂类药物为基础的一线治疗和药物遗传学限制。
在全球所有高发肿瘤中,肺癌的死亡率最高。其一线治疗药物--顺铂的主要问题是化疗耐药性的快速发展和多器官毒性,包括听力下降和耳鸣、肾毒性、肝毒性和骨髓抑制(包括贫血和中性粒细胞减少)。本综述总结了不同基因中单核苷酸多态性(SNP)与上述毒性点相关的研究,以观察药物基因组学模式。特别是 ATP7B、ERCC-1、ERCC-2、MATE-1、OCT-2、ABCB-1、ABCC-1、ABCG-2、ABCC-2、SLC22A、ERCC-5、BRCA-1、GSTM-3、GSTM-4 和 GSTM-5 基因中的 SNP 似乎与顺铂的治疗反应和/或不良反应有关。我们建议利用这些信息最大限度地降低因化疗耐药性和对其他器官的不良影响而导致治疗失败的风险。
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