SNPs in predicting clinical efficacy and toxicity of chemotherapy: walking through the quicksand

Raffaele Palmirotta, Claudia Carella, Erica Silvestris, Mauro Cives, Stefania Luigia Stucci, Marco Tucci, Domenica Lovero and Franco Silvestris _

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Oncotarget. 2018; 9:25355-25382. https://doi.org/10.18632/oncotarget.25256

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Raffaele Palmirotta1, Claudia Carella1, Erica Silvestris1, Mauro Cives1, Stefania Luigia Stucci1, Marco Tucci1, Domenica Lovero1 and Franco Silvestris1

1Department of Biomedical Sciences and Human Oncology, Section of Clinical and Molecular Oncology, University of Bari Aldo Moro, 70124 Bari, Italy

Correspondence to:

Franco Silvestris, email: [email protected]

Keywords: cancer; targeted therapy; chemotherapy; precision medicine; single nucleotide polymorphisms

Received: March 07, 2018    Accepted: April 07, 2018    Published: May 18, 2018


In the “precision medicine” era, chemotherapy still remains the backbone for the treatment of many cancers, but no affordable predictors of response to the chemodrugs are available in clinical practice. Single nucleotide polymorphisms (SNPs) are gene sequence variations occurring in more than 1% of the full population, and account for approximately 80% of inter-individual genomic heterogeneity. A number of studies have investigated the predictive role of SNPs of genes enrolled in both pharmacodynamics and pharmacokinetics of chemotherapeutics, but the clinical implementation of related results has been modest so far. Among the examined germline polymorphic variants, several SNPs of dihydropyrimidine dehydrogenase (DPYD) and uridine diphosphate glucuronosyltransferases (UGT) have shown a robust role as predictors of toxicity following fluoropyrimidine- and/or irinotecan-based treatments respectively, and a few guidelines are mandatory in their detection before therapy initiation. Contrasting results, however, have been reported on the capability of variants of other genes as MTHFR, TYMS, ERCC1, XRCC1, GSTP1, CYP3A4/3A5 and ABCB1, in predicting either therapy efficacy or toxicity in patients undergoing treatment with pyrimidine antimetabolites, platinum derivatives, irinotecan and taxanes. While formal recommendations for routine testing of these SNPs cannot be drawn at this moment, therapeutic decisions may indeed benefit of germline genomic information, when available. Here, we summarize the clinical impact of germline genomic variants on the efficacy and toxicity of major chemodrugs, with the aim to facilitate the therapeutic expectance of clinicians in the odiern quicksand field of complex molecular biology concepts and controversial trial data interpretation.

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