ESTABLISHMENT AND CHARACTERIZATION OF A MODEL OF RESISTANCE TO TOPOTECAN. IMPLICATIONS IN RETINOBLASTOMA TREATMENT

CANCELA, MARÍA BELEN; ZUGBI, SANTIAGO; WINTER, URSULA; SAMPOR, CLAUDIA; FANDIÑO, ADRIANA ; LUBINIECKI FABIANA; CHANTADA, GUILLERMO; CARCABOSO, ANGEL; SCHAIQUEVICH, PAULA

Congreso; Reunión Conjunta de Biociencias 2021; 2021

During the last decades, retinoblastoma (Rb) treatments have changed to local delivery of chemotherapy greatly improving ocular preservation rates. Nevertheless, some eyes develop relapse or recurrence disease probably associated with acquired pharmacological resistance. Our aim was to establish a topotecan-resistant cell subtype (HSJD-RBT-7-TP) as a tool for studying the pharmacological sensitivity to the most common chemotherapy agents and identifying alternative treatments that circumvent resistance. A primary cell culture was established from the tumor biopsy of an upfront enucleated patient with intraocular Rb. The parental cell line (HSJD-RBT-7) was exposed to three weekly doses of topotecan equivalent to the IC50. Once HSJD-RBT-7-TP cells were established, we determined the sensitivity to topotecan, melphalan and carboplatin. Alternative treatments assessed for cytotoxicity in HSJD-RBT-7-TP included 3-weekly doses of high-dose (IC90) topotecan, digoxin exposure and metronomic topotecan. Cell viability was determined using the MTT assay. Mean (range) topotecan IC50 in HSJD-RBT-7-TP cells was 8,1 nM (6,8-9,3), 3-fold higher than that in HSJD-RBT-7 (p