THE MECHANISM OF ACTION AND MECHANISM OF RESISTENCE OCCURENCE IN THE TREATMENT WITH TYROSINE-KINASE INHIBITORS

IULIAN POPESCU, PhD, MD

The Clinical Department of Radiobiology from the Fundeni Clinical Institute,

e-mail: popdociul@yahoo.com

Alina Halpern, PhD,  "Sf. Stefan" Hospital, Bucharest

ABSTRACT

Since 2000 a new era has begun in the treatment of lung adeno-carcinoma (ADC), which will improve, diversify, enrich the chemotherapy treatment of lung cancer (PA) which becomes the targeted treatment for a heterogeneous disease. The tyrosine-kinase inhibitors (ITK) have effect only upon ADC with EGFR mutations.

The most frequent mutations are at the level of the 19th exon  through deletion and at the level of the 21st exon  through punctiform mutations (T858R)

The EGFR and Kopi mutations, after the stimulation of ligands, undergo a homo or heterodimerization, leading to the autophosphorylation of the ATP / EGFR group, which in turn activate the pathways: PI3K/AKT, JAK/STAT and Ras/MAPK which further lead to cellular growth, survival and proliferation. The ITK blocks the ATP- EGFR phosphorylation, leading to the increase of cellular apoptosis. But after a period

THE EPITHELIAL MESENCHYMAL TRANSITION - MAIN FACTORS AND ITS INSTALLATION MECHANISM

POPESCU IULIAN, PhD, MD,

The Radiobiology Department of the Clinical Institute in Fundeni Bucharest

E-mail: popdociul@yahoo.com

ALINA HALPERN, PhD "St. Stefan" Hospital, Bucharest

ABSTRACT

The metastatic progression is responsible for most deaths from cancer in humans. For achieving this it is necessary to convert the epithelial phenotype of cancer cells into the mesenchymal phenotype that favours metastasis. This transformation, which is transient, is called Epithelial-Mesenchymal Transition (EMT).

The epithelial cancerous cells are characterized by immobility, apical-basal polarity, strong junctions of desmozomes, an interaction between the cell and extracellular matrix and an increased expression of cell adhesion markers, where E-cadherin plays the main role.

The mesenchymal cell is mobile, multi-polar, fusiform aspect, does not make strong cell-cell contacts, it can invade and express multiple markers, which confers these properties.

The TEM process is a complex mechanism involving changes in the expression, distribution and /or function of several proteins. Among the main factors, we distinguish: