Associação Portuguesa de Investigação em Cancro
Estudos pré-clínicos sobre o efeito antitumoral e não tóxico da associação de pirfenidona com vinorelbina e carboplatina no cancro do pulmão de não pequenas células
Estudos pré-clínicos sobre o efeito antitumoral e não tóxico da associação de pirfenidona com vinorelbina e carboplatina no cancro do pulmão de não pequenas células
Este trabalho, recentemente publicado no “International Journal of Cancer”, demonstrou a possibilidade de reposicionar a pirfenidona (um fármaco antifibrótico) em combinação com vinorelbina ou com vinorelbina mais carboplatina para o tratamento perioperatório do cancro do pulmão de não pequenas células (CPNPC), com o objetivo de melhorar a eficácia terapêutica e reduzir a toxicidade. Este trabalho resultou de uma colaboração entre o grupo Cancer Drug Resistance do i3S e o Grupo de Patologia Experimental e Terapêutica do IPO Porto.
Autores e Afiliações:
Helena Branco - i3S – Instituto de Investigaçao e Inovação em Saúde, Universidade do Porto, Porto, Portugal; Cancer Drug Resistance Group, IPATIMUP - Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal
Catarina A. Rodrigues - i3S – Instituto de Investigaçao e Inovação em Saúde, Universidade do Porto, Porto, Portugal; Cancer Drug Resistance Group, IPATIMUP - Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal; Experimental Pathology and Therapeutics Group, IPO—Instituto Português de Oncologia, Porto, Portugal
Júlio Oliveira - Experimental Pathology and Therapeutics Group, IPO—Instituto Português de Oncologia, Porto, Portugal
Nuno Mendes - i3S – Instituto de Investigaçao e Inovação em Saúde, Universidade do Porto, Porto, Portugal; HEMS—Histology and Electron Microscopy, i3S—Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
Catarina Antunes - i3S – Instituto de Investigaçao e Inovação em Saúde, Universidade do Porto, Porto, Portugal; Cancer Drug Resistance Group, IPATIMUP - Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal
Irina Amorim - i3S – Instituto de Investigaçao e Inovação em Saúde, Universidade do Porto, Porto, Portugal; Glycobiology in Cancer Group, IPATIMUP—Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal; ICBAS-UP—School of Medicine and Biomedical Sciences, University of Porto, Porto, Portugal
Lúcio L. Santos - Experimental Pathology and Therapeutics Group, IPO—Instituto Português de Oncologia, Porto, Portugal; ICBAS-UP—School of Medicine and Biomedical Sciences, University of Porto, Porto, Portugal
M. Helena Vasconcelos - i3S – Instituto de Investigaçao e Inovação em Saúde, Universidade do Porto, Porto, Portugal; Cancer Drug Resistance Group, IPATIMUP - Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal; Department of Biological Sciences, FFUP –Faculty of Pharmacy, University of Porto, Porto, Portugal
Cristina P. R. Xavier - i3S – Instituto de Investigaçao e Inovação em Saúde, Universidade do Porto, Porto, Portugal; Cancer Drug Resistance Group, IPATIMUP - Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal; UCIBIO—Applied Molecular Biosciences Unit, Toxicologic Pathology Research Laboratory, University Institute of Health Sciences (1HTOXRUN, IUCS-CESPU), Gandra, Portugal; Associate Laboratory i4HB—Institute for Health and Bioeconomy, University Institute of Health Sciences—CESPU, Gandra, Portugal
Abstract:
Non-small cell lung cancer (NSCLC) shows limited therapeutic response to vinorelbine and carboplatin. Combining these drugs with an antifibrotic drug may enhance their antitumor effect. Pirfenidone is an antifibrotic drug whose antitumor activity has been described in different types of cancer. This work aimed to perform preclinical studies on the combination of pirfenidone with vinorelbine, or with vinorelbine plus carboplatin, in NSCLC. Our data revealed that pirfenidone sensitized three NSCLC cell lines to vinorelbine by reducing cell growth, viability and proliferation, inducing alterations in the cell cycle profile, and increasing cell death (%). Importantly, pirfenidone increased the sensitivity of the three NSCLC cell lines to the combined treatment of vinorelbine plus carboplatin. This combined drug treatment (triplet) did not induce cytotoxicity against non-tumorigenic cells. Notably, the triplet drug combination significantly reduced the growth and proliferation of A-549 xenografts in nude mice, as also reduced vimentin and collagen expression. Most interestingly, the triplet treatment exhibited a safer toxicological profile than the doublet (vinorelbine plus carboplatin) currently applied in the clinical practice. Altogether, these preclinical data support the possibility of repurposing pirfenidone in combination with vinorelbine or with vinorelbine plus carboplatin for NSCLC perioperative treatment, improving therapeutic efficacy while reducing toxicity.
Revista: International Journal of Cancer
