Prof. Renata Dobrila-Dintinjana is a physician, specialist in internal medicine, subspecialist in medical oncology, Professor at Faculty of Medicine University Rijeka.Her research focused on field of gastrointestinal tumours and supportive cancer care, specially in the field of cachexia-anorexia syndrome and nutrition. She is author of over 100 publications , 2 books, 20 chapters in the book and over 300 abstracts. Member of ASCO, ESMO, AACR, MASCC, IASGO, member and head of some Executive Boards in Croatia and reviewer for journals and projects in the field of Supportive Cancer Care, Palliative Care, Gastrointestinal Cancers and Molecular Oncology.
Colorectal cancer (CRC) is a heterogeneous disease with increasing incidence and is the third most common cancer worldwide. 80% of CRC cases are sporadic without family history or genetic predisposition as a result of agglomeration of mutations and epigenetic modifications of several genes together with environmental factors. Chemotherapy together with targeted drugs tending to individualized therapy is a cornerstone of systemic treatment. Molecular and genetic features of the tumor determine the prognosis and response to (targeted) treatments. Anemia of chronic disease can be found in about 60-70% of patients with malignant disease. Pathophysiology of this type of anemia is multifactorial and level of hemoglobin is independent bad prognostic factor for survival. Anemia in malignant disease is often cured with recombinant erythropoietin (rHuEpo). Epo is a 34-kDa glycoprotein hormone, who binds to cells with erythropoietin receptor (EpoR), thus leading to its activation and stimulation of erythropoiesis. Basic mechanism of action on which Epo stimulates erythropoiesis is preventing programmed cell death. EpoR is a protein, member of the cytokine receptor family, which expression was found in different tumors.
The role of Epo/EpoR signaling pathway in CRC remains unclear and data from studies are inconclusive. Moreover, the data in vivo are not consistent with those in vitro suggesting that Epo in vivo is probably acting together with other growth factors. Because there is still no conclusive answer does rHuEpo therapy leads to tumor progression, clinicians can use it only in limited frameworks. Especially precaution must be taken using rHuEpo together with anticancer drugs (numerous!) which are using activation of NF-kB to kill cancer cells due to association of Epo and protein NF-kB in apoptotic resistance, thus leading to negative effect of anticancer therapy .
For elucidating the role of Epo/EpoR system in CRC and other tumors, standard procedures for detection of receptor-specific antibodies, for binding of radiolabeled ligands and confirmation of receptor size at the appropriate molecular mass must be followed. Even after such a use with all precautions, limitations in these techniques can possibly lead to a contradictory and inconclusive data. The preliminary data of our study with 145 colorectal carcinoma tissue specimens, 50 adenoma tissue specimens and 50 healthy controls tissue specimens, are showing quite confusing data. EPO was moderate expressed in carcinoma/adenoma tissues (87% and 86% respectivelly) versus 56% of healthy controls, EpoR was highly expressed in 25,5% of carcinoma sampes, 20% in adenoma samples but in healthy controls 94%. CD31 was statistically significant higher in tissue samples of healthy persons (P< 0,001) and mean values of CD31 were also significantly higher in Dukes A tumors. The moderate expression of EPO was conducted with more local recidives and metastatic disease (P<0,001). We can conclude that is necessary to perform more studies for elucidating the real role of Epo/EpoR system in this highly malignant disease.
For audience: there is a huge need for development of more biomarkers who will directthe diagnostic and therapy to more individual approach. Altough is Epo/EpoR system in majority of cancers mostly connected to worse disease outcome and faster disease progression, for colorectal cancer the data are still inconclusive. Our study shows connection of Epo expression and local recidives. Therefore, we can speculate that colorectal cancer biology is much more different than in other tumors.