Researchers at Tumor angiogenesis group at Bellvitge Biomedical Institute of Research (IDIBELL) and the Catalan Institute of Oncology (ICO) led by Francesc Viñals have published a study in the journal Clinical Cancer Research where they propose an alternative treatment to cisplatin resistant testicular cancer patients .
90 % cure rate of testicular tumors
Testicular tumor has a cure rate of 90 % as it has a relatively simple surgery and because is the most responsive to chemotherapy tumor, especially to cisplatin . However, there is a percentage of more aggressive tumors which are metastatic . Among these , 80% are cured but also other are resistant to cisplatin directly (refractory patients ¡) or acquire resistance to the drug (patients with acquired resistance).
The Francesc Viñals team is working for years to find therapeutic alternatives for these patients using pre-clinical models of these testicular tumors. Results of the group indicate a clear anti -tumor effect by both ant -angiogenic and anti-drug receptors like the EGF family of combination cisplatin refractory models.
In recent years the team of Viñals has focused on studying the molecular mechanisms leading to tumor cells of coreocarcinoma (an aggressive type of testicular cancer) to acquire this chemoresistance to cisplatin . “Some cells are able to clear the route of entry of cisplatin or to detoxify drugs. There are various adaptations . We have studied the cellular response that involves activating signaling pathways that estimulna the survival of the cell.”
Survival signaling pathway
“The cell interpreted cisplatin as and aggression and they active mechanisms to counteract this signal: secretes growth factors that stimulate survival and survival pathways.One of these pathways is the PI3quinasa – AKT ” said Viñals .
In this work, researchers have observed that the recipient of one of these factors activates via PI3quinasa – AKT , the PDGFRbeta has very high levels both in patients with coreocarcinoma cisplatin-resistant in cell lines and mice resistants.
” Currently ” explained Vinyals ” there are drugs on the market that block the PDGF receptor and we have seen in cell lines and in mice that when the cell returns to normal levels , also gets the sensitivity to cisplatin . Therefore our proposal for patients with resistant coreocarcinoma is to give these drugs but continue with cisplatin to manage non stop fighting against the tumor . ”
Although these drugs are already used in the clinic, the next step of Viñals group would be to conduct a clinical trial to test the alternative also works in humans. “The problem is funding,” says researcher ” and we need to generate interest in the pharmaceutical industry and considering that testicular cancer is not considered a ‘big kiler ‘ is difficult. In my opinion, in these cases public institutions should take responsibility perhaps through a European agency that would be responsible for assessing new therapeutic proposals and funding to be transferred to the clinic. ”
M. Juliachs , C. Muñoz , C. A. Moutinho , A. Vidal , E. Condom, M. Esteller, M. Graupera , O. Casanovas , J. R. Brother, A. Villanueva and F. Viñals . The PDGFRβ – AKT Pathway To CDDPAcquired taxable Testicular Germ Cell Resistance In tumors . Clincanres.1131.2013 Clincal Cancer Research .
Juliachs M , Castillo – Avila W , Vidal A, Piulats JM , Garcia Del Muro X , Condom E, Hernández- Losa J , Teixidó C , Pandiella A, Graupera M , Casanovas O , Brother JR , Villanueva A, Viñals F. ErbBs inhibition by lapatinib blocks tumor growth in an orthotopic model of human testicular germ cell tumor. International Journal of Cancer 133: 235-246 , 2013.
Juliachs M , Vidal A, Del Muro XG , Piulats JM , Condom E, Casanovas O, Graupera M , Brother JR , Villanueva A, Viñals F. Effectivity of pazopanib treatment in orthotopic models of human testicular germ cell tumors. BMC – Cancer 13 : 382 , 2013 .