Personalised medicine in solid tumours
In Europe, prostate cancer (PCa) is the most common solid organ malignancy, with an incidence of 214 cases per 1000 men, surpassing the numbers for lung and colorectal cancers. PCa most frequently affects the elderly and is therefore a major health problem in developed countries. Therapeutic management of PCa has become increasingly complex as a result of the availability of different stage-specific therapeutic options.
Discrimination between favourable and unfavourable intermediate risk diseases is a major issue. Especially important is the identification of high-risk patients (based on clinical and molecular patterns), susceptible to more intense and radical treatment or inclusion in clinical trials. Since advanced PCa may be considered a chronic disease, quality of life assessment and control of treatment-induced toxic effects have become a priority in the global approach to PCa patients.
This group is focused on three lines of research: 1) Identifying clinical and biological markers as risk and predictive factors. We are working on a cooperation project with the CNIO to determine the prognostic value of molecular marker expression (hif1a, pak-6, and psmb4) in biopsy samples from patients with intermediate- and high-risk localised prostate cancer, treated with androgen deprivation therapy and dose-escalated radiotherapy.
We also took part in an international project with a panel of cell cycle progression genes (CCP); a test for risk assessment in patients with localised PCa. The test combines the expression levels of 31 genes related to cell cycle progression and 15 housekeeping genes into a cell cycle progression index (CCP) that will be used to predict prostate cancer-specific progression and mortality over 10 years. 2) Randomised trials over the past two decades have shown that androgen deprivation therapy combined with conventional radiotherapy doses improves overall survival, primarily in patients with intermediate- and high-risk prostate cancer.
Similarly, clinical outcomes have improved substantially with high-dose radiotherapy. In view of the absence of specific randomised trials, we designed a phase III clinical trial to determine the optimal duration of androgen deprivation therapy, along with high-dose radiotherapy in intermediate- and high-risk localised PCa patients (EudraCT 2005-000417-36). 3) The androgen receptor continues to be the primary cause of CRPC progression. We took part in two international clinical trials using Enzalutamide. Enzalutamide is a potent androgen receptor inhibitor that significantly prolongs overall survival in men with metastatic CRPC. The two trials will evaluate Enzalutamide in two scenarios: CRPC and biochemical progression treatment after local primary therapy.
Almudena Zapatero Laborda
Hospital Universitario La Princesa
| Other team members. Hospital Universitario La Princesa:
Zapatero A, García-Vicente F, Martín de Vidales C, Cruz Conde A, Ibáñez Y, Fernández I, Rabadán M. Long-term results after high-dose radiotherapy and adjuvant hormones in prostate cancer: how curable is high-risk disease? Int. J. Radiat. Oncol. Biol. Phys. 2011. 81: 1279-1285. FI: 4.105(Q1). PMID: 22999456. DOI: 10.1016/j.urology.2012.07.045.
Zapatero A, Mínguez R, Nieto S, Martín de Vidales C, García-Vicente F. Post-treatment prostate biopsies in the era of three-dimensional conformal radiotherapy: what can they teach us?. Eur Urol 2009. 55:902-909. FI: 7.667(Q1). PMID: 18485578. DOI: 10.1016/j.eururo.2008.04.076.
Zapatero A, Valcárcel F, Calvo FA, Algás R, Béjar A, Maldonado J, Villá S. Risk-adapted androgen deprivation and escalated three-dimensional conformal radiotherapy for prostate cancer: Does radiation dose influence outcome of patients treated with adjuvant androgen deprivation? A GICOR study. J Clin Oncol 2005. 23:6561-6568. FI: 11.810 (Q1). PMID: 16170164.
Zapatero A, Morente M, Nieto S, Martín de Vidales C, Lopez C, Adrados M, Arellano R, Artiga MJ, Garcia-Vicente F, Herranz LM, Leaman O. Predictive value of PAK6 and PSMB4 expression in patients with localized prostate cancer treated with dose-escalation radiation therapy and androgen deprivation therapy. Urol. Oncol.-Semin. Orig. Investig. 2014. 32: 1327-1332. FI: 2.768(Q2). PMID: 24946957. DOI: 10.1016/j.urolonc.2014.05.004.