Despite the relative low incidence, when compared to other lung tumors, Small cell lung carcinoma (SCLC) is the most aggressive subtype, with high capacity of growth and dissemination. About 30% of patients diagnosed with SCLC do not respond to first line chemotherapy and relapse within 6 months. Mechanisms of tumor escape are still unknown, however they can involve: i) rapid evolution and selection of resistant cancer cells - with increased mutational capacity- in response to chemotherapeutics; and ii) mechanisms of immune escape/modulation. Genetic modifications in the primary tumor can be detected in the blood and other body fluids, allowing a non-invasive evaluation of these circulating components (liquid biopsy) and the analysis of the tumor genetic dynamics, which might reveal chemotherapy resistance mechanisms and can help identifying cancer progression markers. Studies have suggested that liquid biopsy elements carry predictive information of response and relapse that can be detected prior to the treatment initiation of SCLC patients. On the other hand, an even more valuable data can be generated integrating other biological aspects, such as inflammatory markers, systemic immune status, tumor-infiltrating immune cell profiles and pulmonary microbiome alterations. Altogether, this integrative approach can potentially identify drug resistance markers and better untangle chemoresistance mechanisms in SCLC. Based on that, this proposal aims to identify biological alterations that can be used as therapy resistance markers in patients diagnosed with SCLC, validate those markers in two independent cohorts and further evaluate these alterations during the entire therapeutic process, intending to integrate the information gathered with therapy response.
News published in Agência FAPESP Newsletter about the scholarship: