LungSys

“Systems Biology” A novel approach to The Lung Cancer Problem

- Preventing the Risk of Epo Treatment

Cancer is one of the leading causes of death worldwide with 7.4 millions per year, and it is predicted to reach up to 12 millions for 2030 (1). Lung cancer is the most common cause of cancer deaths with 1.3 millions per year, representing 13% of the total deaths by cancer. Around 80% of the lung cancer cases are identified as Non Small Cell Lung Carcinoma (NSCLC) and most of them can be classified into Squamouscarcinoma group or Adenocarcinoma group. Both cancer types are developed from the cells that line the airways in the bronchus.

Once the diagnosis is made, chemotherapy is one of the most common components of the therapeutic and palliative treatments that the lung cancer patients will receive. As side effect of these treatments, there is commonly an anemia associated to the chemotherapy. This reduces the patient quality of live and sometimes forces the interruption of the treatments. In order to avoid this anemia, the stimulation of the erythrocytes (red cells) synthesis is considered as a straight approach. This might be achieved by the use of recombinant erythropoietin (Epo) that induces the production and differentiation of erythrocytes by the bone marrow of the patient, reestablishing the normal levels of oxygen supplies to the body.

Over the last decade, Epo receptors (EpoR) have been found in some tumor cell lines (2), lung tumors (3) and a clinical trial (4) showed a worse progression-free survival in the patients treated with Epo. Therefore, to ensure safety of the treatment and improve quality of life of patients, an important question is to clarify the role of the EpoR in lung cancer. But since the outcome is influenced by the dynamic interplay of many components, it has to be addressed from multiple angles and requires quantitative experimental studies at different levels. These different perspectives go from molecular studies of EpoR activation in a single tumor cell to the study of angiogenesis process of the tumor mass in the lung by medical imaging. Due to the complexity, non-linear relationship and involvement of multiple scales, this requires a Systems Biology approach that combines experimental data generation and mathematical modeling.

The need to improve the safety of Epo treatment of anemia associated with chemotherapy in cancer patients, encouraged clinicians and basic researcher of multiple disciplines to join efforts in the consortium LungSys funded in the MedSys call by the German Ministry of Education and Research. The aim of the LungSys consortium is to identify the effects of EPO treatments in cancer cells from the protein level to organ level, integrating the experimental data in a multi-scale model using a Systems Biology approach, and designing strategies to avoid anemia associated with chemotherapy.

References:

  • (1)-World Health Organization Web Site.
    www.who.int/mediacentre/factsheets/fs297/en/
  • (2)- Yasuda Y, Fujita Y, Matsuo T, Koinuma S, Hara S, Tazaki A, et al. Erythropoietin regulates tumour growth of human malignancies. Carcinogenesis 2003: 24, 1021-9.
  • (3)-Dagnon K, Pacary E, Commo F, et al. Expression of erythropoietin and erythropoietin receptor in non-small cell lung carcinomas. Clin Cancer Res 2005;11(3):993-9.
  • (4)-Wright JR, Ung YC, Julian JA, et al. Randomized, double-blind, placebo-controlled trial of erythropoietin in non-small-cell lung cancer with disease-related anemia. J Clin Oncol 2007;25(9):1027-32.