Abstract 435: Prognostic biomarkers as molecular targets for individualized neoadjuvant treatment for cervical cancer
Authors: Pablo Moreno-Acosta, Oscar Gamboa, Diana Mayorga, Alfredo Romero, Jinneth Acosta, Maria Carolina Sanabria, Martha Cotes Mestre, Nicolas Magne
Journal: Cancer Research (2016)

Abstract Cervical cancer is one of the most prevalent malignancy and of higher mortality in the world, and is considered a marker of underdevelopment. Conventional radiotherapy is one of the treatments used for this type of cancer. 30 to 40% of patients with similar prognosis factors not respond equally to a comparable standard treatment. The poor response to radiotherapy leads to the development of innovative and effective therapies for cervical cancer locally advanced, metastatic and refractory. A comparative analysis of cervical cancer in the context of other cancers may reveal that it is relatively smaller number of targeted molecular agents that have been tested. Accordingly, a number of biological agents are currently in clinical development for the purpose of, inhibiting angiogenesis, molecularly address EGFR and IGF-1R, modulation of cell cycle, of histone deacetylases, COX-2, mTOR and tumor microenvironment (hypoxia and glycolysis). Within work that we have been developing, reported that gene expression of IGF1R is a strong predictive marker for lack of response to radiotherapy, patients have 28.6 times higher risk of failure treatment; Objective: To determine whether expression of IGF-IR, GAPDH, HIF-1 alpha, Survivin, GLUT1, CAIX, HKII and clinicopathological parameters can be used as prognostic biomarkers to treatment outcome and as possible molecular targets. Patients &amp; Methods: This prospective cohort study included 149 patients with squamous cell carcinomas of the uterine cervix in FIGO stages IIB and IIIB between 2008 and 2011. The mean age was 46 years. Of the 149 patients, 61 were treated with radiotherapy and 88 with concurrent radiochemotherapy. Expression of the proteins CAIX, GLUT-1, HIF1α, HKII, IGF-IRα, IGF-IRβ and Survivin was determined by immunohistochemistry in biopsies taken before treatment. Results: The highest increase was found in expression of GAPDH (100%), Survivin (87%), followed of, IGF-IRα (76.5%), IGF-IRβ (74.5%), IGF-IRα and IGF-IRβ concordance in the expression(73%), HIF1α (74.1%); strong expression was observed with low frequency for GLUT-1 (31.1%), CAIX (16.2%), HKII (10.6%). We found that patients who do not express IGF-1Rß, GLUT1 and having hemoglobin levels &amp;gt; 11g/dl have improved overall survival compared to those that express IGF-1Rß, GLUT1 and having hemoglobin ≤ 11g/dl (P = 0.0158). Conclusions: Using the expression of GLUT1, IGF-1Rß and Hb levels (≤ 11g/dl) as therapeutic molecular targets could contribute to an appropriate therapeutic management as individualized neoadjuvant treatment for cervical cancer Citation Format: Pablo Moreno-Acosta, Oscar Gamboa, Diana Mayorga, Alfredo Romero, Jinneth Acosta, Maria Carolina Sanabria, Martha Cotes Mestre, Nicolas Magne. Prognostic biomarkers as molecular targets for individualized neoadjuvant treatment for cervical cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 435.