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Journal of Thoracic Disease (1)
Translational Lung Cancer Research (1)
Bonanno, Laura (3)
Altavilla, Giuseppe (1)
Costa, Carlota (1)
Favaretto, Adolfo (1)
Favaretto, Adolfo Gino (1)
Gimenez-Capitan, Ana (1)
Majem, Margarita (1)
Massuti, Bartomeu (1)
Pallares, Cinta (1)
Pasello, Giulia (1)
Rea, Federico (1)
Rodriguez, Ignacio (1)
Rosell, Rafael (1)
Rugge, Massimo (1)
Sanchez, Jose Javier (1)
Taron, Miquel (1)
Vergenegre, Alain (1)
Year of Publication
The predictive value of 53BP1 and BRCA1 mRNA expression in advanced non-small-cell lung cancer patients treated with first-line platinum-based chemotherapy
Sanchez, Jose Javier
Platinum-based chemotherapy is the standard first-line treatment for non-oncogene-addicted non-small cell lung cancers (NSCLCs) and the analysis of multiple DNA repair genes could improve current models for predicting chemosensitivity. We investigated the potential predictive role of components of the 53BP1 pathway in conjunction with BRCA1. The mRNA expression of BRCA1, MDC1, CASPASE3, UBC13, RNF8, 53BP1, PIAS4, UBC9 and MMSET was analyzed by real-time PCR in 115 advanced NSCLC patients treated with first-line platinum-based chemotherapy. Patients expressing low levels of both BRCA1 and 53BP1 obtained a median progression-free survival of 10.3 months and overall survival of 19.3 months, while among those with low BRCA1 and high 53BP1 progression-free survival was 5.9 months (P <0.0001) and overall survival was 8.2 months (P=0.001). The expression of 53BP1 refines BRCA1-based predictive modeling to identify patients most likely to benefit from platinum-based chemotherapy.
BRCA1; 53BP1; DNA repair; predictive modeling; platinum
Predictive models for customizing chemotherapy in advanced non-small cell lung cancer (NSCLC)
Translational Lung Cancer Research
The backbone of first-line treatment for Epidermal Growth Factor (EGFR) wild-type (wt) advanced Non-small cell lung cancer (NSCLC) patients is the use of a platinum-based chemotherapy combination. The treatment is characterized by great inter-individual variability in outcome. Molecular predictive markers are extremely needed in order to identify patients most likely to benefit from platinum-based treatment and resistant ones, thus optimizing chemotherapy approach in NSCLC. Several components of DNA repair response (DRR) have been investigated as potential predictive markers. Among them, high levels of expression of ERCC1, both at protein and mRNA levels, have been associated with resistance to cisplatin in NSCLC. In addition, low levels of expression of RRM1, a target for gemcitabine, have been associated with improved OS in advanced NSCLC patients treated with cisplatin and gemcitabine. Preclinical data and retrospective analyses showed that BRCA1 is able to induce resistance to cisplatin and sensitivity to antimicrotubule agents. In addition, the mRNA levels of expression of RAP80, encoding for a protein cooperating with BRCA1 in homologous recombination (HR), have demonstrated to further sub-classify low BRCA1 NSCLC tumors, improving the predictive model. On the basis of biological knowledge on DNA repair pathway and recent controversial results from clinical validation of potential molecular markers, integrated analysis of multiple DNA repair components could improve predictive information and pave the way to a new approach to customized chemotherapy clinical trials.
Platinum; ercc1; brca1; dna repair; predictive modeling
A pathological complete response after preoperative chemotherapy with carboplatin and pemetrexed in malignant pleural mesothelioma: A case report.
Favaretto, Adolfo Gino
Journal of Thoracic Disease
Malignant pleural mesothelioma is an aggressive tumour with poor prognosis and short duration of response probably due to the high chemo-refractoriness. Multimodality treatment based on preoperative chemotherapy, surgery and adjuvant radiotherapy seems to be a feasible and effective therapeutic option in selected patients.We report on a case of pathological complete response in a patient affected by malignant pleural mesothelioma who was treated with four cycles of preoperative chemotherapy based on carboplatin plus pemetrexed followed by parietal pleurectomy and lung decortication. Carboplatin plus pemetrexed was a well tolerated regimen without grade 3-4 haematological toxicity, and this confirm the feasibility of such a treatment as an alternative to the current golden standard based on cisplatin plus pemetrexed.Complete resection allows the pathologist to better describe biological markers of mesothelioma cells, in order to select patients with different treatment outcome and prognosis.
mesothelioma; chemotherapy; carboplatin; pemetrexed
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