Abstract 4314: Prediction of chemotherapy response and metabolism for the tailoring of ovarian cancer treatment
Authors: Maria Loreto Bravo, Pamela Gonzalez, Sumie Kato, Carolina Ibañez, Marcelo Garrido, Jorge Brañes, Maria Isabel Barriga, Eva Bustamante, Nicanor Barrena, Catalina Alonso, Leonel Muñoz, Erasmo Bravo, Clemente Arab, Alejandro Barra, Paula Jimenez, Patricio Gayan, Fernando Gonzalez, Ignacio Chavez, Alfredo Aguilar, Joseph Pinto, Mauricio Cuello, Gareth Owen, Jaime Cartagena
Journal: Cancer Research (2015)

Abstract Ovarian cancer patients respond well to first line chemotherapy but present high incidences of toxicity followed by consistent relapse within 18 months. Despite every cancer and patient being unique, generally all cancers are treated by the same chemotherapy regimes and patient metabolism is not considered in treatment selection. Differing metabolism may account for unacceptable toxicity or failures in chemotherapy treatment. It is becoming accepted that the metastatic cell is distinct to those found in the primary tumor and is thus the true target of chemotherapy. Our objectives were to isolate these potential ovarian metastatic cells from patients and correlate their in vitro response to the chemotherapy with clinical response. The single nucleotide polymorphism (SNP) distribution of genes related to chemotherapy metabolism was also analyzed in each patient. Primary cultures and blood samples of ovarian patients were obtained with signed informed consent from a network of Chilean and Peruvian hospitals. Chemotherapy response was assessed by MTS and data correlated with medical follow-up. SNPs were detected using commercial taqman probes from Applied Biosystem. Results. Ovarian cancer patients with clinical follow-up demonstrated a marked separation of progression free survival (PFS) curves according to classification within our in vitro assay. Analysis of exclusively first line patients demonstrated a median PFS of 17 months for patients predicted to respond to treatment showed by our assay, but only an average of 2 months of PFS in patients that the assay predicted no response. Initial analysis of 14 SNPs related to paclitaxel-platinum based chemotherapy demonstrates marked differences in Chilean patients. Conclusion. We demonstrate a clear distinction in time to relapse between the patients predicted or not to respond to treatment by our assay. Ovarian cancer patients demonstrate notably different distributions in SNPs previously correlated with platinum metabolism. Our results highlight the requirement of the medical community to take this research to the stage of randomized clinical trials. CORFO 13CTI21526-P6 &amp; 13IDL2-18608, FONDECYT 1140960, 1140657 &amp; 1120292. Citation Format: Maria Loreto Bravo, Pamela Gonzalez, Sumie Kato, Carolina Ibañez, Marcelo Garrido, Jorge Brañes, Maria Isabel Barriga, Eva Bustamante, Nicanor Barrena, Catalina Alonso, Leonel Muñoz, Erasmo Bravo, Clemente Arab, Alejandro Barra, Paula Jimenez, Patricio Gayan, Fernando Gonzalez, Ignacio Chavez, Alfredo Aguilar, Joseph Pinto, Mauricio Cuello, Gareth Owen, Jaime Cartagena. Prediction of chemotherapy response and metabolism for the tailoring of ovarian cancer treatment. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4314. doi:10.1158/1538-7445.AM2015-4314