Original Articles: Basic ScienceProliferation index and pseudoprogression as predictors of the therapeutic efficacy of suicide gene therapy for canine melanomaFondello, Chiara*,; Agnetti, Lucrecia*,; Glikin, Gerardo C.; Finocchiaro, Liliana M.E.Author Information Gene Transfer Unit, Institute of Oncology Angel H. Roffo, University of Buenos Aires, Buenos Aires, Argentina * Chiara Fondello and Lucrecia Agnetti contributed equally to the writing of this article. Received 11 August 2018 Accepted 7 December 2018 Correspondence to Liliana M.E. Finocchiaro, PhD, Unidad de Transferencia Genética, Instituto de Oncología Ángel H. Roffo, Universidad de Buenos Aires, Av. San Martín 5481, 1417 Buenos Aires, ArgentinaTel: +54 115 287 5300; e-mail: firstname.lastname@example.org Melanoma Research: April 2020 - Volume 30 - Issue 2 - p 126-135 doi: 10.1097/CMR.0000000000000567 Buy Metrics Abstract In our veterinary clinical trials, the combination of systemic immunotherapy with local herpes simplex virus thymidine kinase/ganciclovir suicide gene (SG) treatment induced tumor pseudoprogression as part of a strong local antitumor response. This phenomenon could be owing to tumor inflammation, increased vascular permeability and to different tumor growth rates before, during and after SG therapy. The proliferation index (PI: the fraction of viable cells in S, G2/M, and hyperdiploid phases) would reflect the in-vivo and in-vitro proportion of proliferating melanoma cells in the absence of treatment (PIB) or in response to SG (PISG). The extent of in-vivo and in-vitro melanoma cells responses to SG exhibited a reverse correlation with PIB and a direct correlation with PISG. Then, the final SG outcome depended on the balance between PIB-dependent ‘regrowth resistance’ versus ‘regrowth sensitivity’ to SG treatment. In all the cell lines derived from canine tumors presenting partial responses to SG treatment, PISG prevailed over PIB. Conversely, as more aggressive was the tumor (greater PIB of the cell line), the more the balance displacement towards ‘regrowth resistance’ over SG ‘regrowth sensitivity’. All these parameters could have a prognostic value for SG treatment response and provide a glimpse at the clinical benefit of this therapy. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.