ERCC1 and ERCC2 Polymorphisms Predict the Efficacy and Toxicity of Platinum-Based Chemotherapy in Small Cell Lung Cancer
Barba Joaquin, Andrés (Institut de Recerca Sant Pau)
López Vilaró, Laura (Institut de Recerca Sant Pau)
Ferre, Malena (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Majem Tarruella, Margarita (Institut de Recerca Sant Pau)
Martínez-Recio, Sergio (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Bell, Olga (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Arranz, María Jesús (Fundació Docència i Recerca Mútua Terrassa)
Salazar, Juliana (Institut de Recerca Sant Pau)
Sullivan, Ivana (Institut de Recerca Sant Pau)
Universitat Autònoma de Barcelona

Date:	2024
Abstract:	Standard first-line chemotherapy in small cell lung cancer (SCLC) is based on the platinum plus etoposide combination. Despite a high objective response rate, responses are not durable and chemotherapy-induced toxicity may compromise treatment. Genetic variants in genes involved in the DNA-repair pathways and in etoposide metabolization could predict treatment efficacy and safety and help personalize platinum-based chemotherapy. Germline polymorphisms in XRCC1, ERCC1, ERCC2, ABCB1, ABCC3, UGT1A1 and GSTP1 genes were investigated in 145 patients with SCLC. The tumor expression of ERCC1 was determined using immunohistochemistry, and the tumor expression of ERCC1-XPF was determined via a proximity ligation assay. Survival analyses showed a statistically significant association between the ERCC1 rs11615 variant and median progression-free survival (PFS) in patients with limited-stage (LS) SCLC (multivariate: hazard ratio 3. 25, [95% CI 1. 38-7. 70]; p = 0. 007). Furthermore, we observed differences between the ERCC1-XPF complex and median PFS in LS-SCLC, although statistical significance was not reached (univariate: positive expression 10. 8 [95% CI 4. 09-17. 55] months versus negative expression 13. 3 [95% CI 7. 32-19. 31] months; p = 0. 06). Safety analyses showed that the ERCC2 rs1799793 variant was significantly associated with the risk of grade ≥ 3 thrombocytopenia in the total cohort (multivariate: odds ratio 3. 15, [95% CI 1. 08-9. 17]; p = 0. 04). Our results provide evidence that ERCC1 and ERCC2 variants may predict the efficacy and safety of platinum-based chemotherapy in SCLC patients. LS-SCLC patients may benefit most from ERCC1 determination, but prospective studies are needed.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	ERCC1 ; ERCC2 ; Pharmacogenomics ; Platinum-based chemotherapy ; Small cell lung cancer
Published in:	Pharmaceutics, Vol. 16 Núm. 9 (september 2024) , p. 1121, ISSN 1999-4923

DOI: 10.3390/pharmaceutics16091121
PMID: 39339159

14 p, 2.6 MB

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