Vol 6, No 2 (2010)
Review paper
Published online: 2010-06-25
Molecular factors in individualisation of chemiotherapy in non-small cell lung cancer - is it far future or close present?
Onkol. Prak. Klin 2010;6(2):62-72.
Abstract
The individualization of systemic therapy in advanced non-small cell lung cancer (NSCLC) becomes fact.
Recently, chosen of therapy's methods were depended on histopathological diagnosis, stage of disease
and patients' performance status. However, the percentage of patients with resistance to chemotherapy was
high. Currently, it was shown that molecular factors may determine treatment efficacy. The high expression
of excision repair cross complementing group 1 (ERCC1) enzyme, which recognizes DNA damage, is unfavorable
predictive factors in platinium-based therapy. High activity of subunit M1 of ribonucleotide reductase
(RRM1) is connected with the resistance to gemcitabine treatment. Among the all mechanisms regarding the
resistance to anti-tubulin agents (vinca alkaloids and taxanes), the overexpression of class III β-tubulin is of
particular interest. Folate analogous - pemetrexed - works by inhibiting enzymes (thymidylate synthase,
dihydrofolate reductase and glycinamide ribonucleotide formyltransferase) used in purine and pyrimidine
synthesis. The favourable role of EGFR gene mutations during therapy with the tyrosine kinase domain inhibitors
is unquestionable. However, the predictive role of EGFR gene amplification in these therapies is receding
into the background. The level of ICAM and VEGF in serum as well as polymorphism of VEGF, ICAM and
IL-8 genes could be practical predictive factors for bevacizumab therapy. Presently, the estimation of several
predictive factors (e.g. mutation in EGFR gene) is used in routine diagnostic during qualification into specific
treatment in lung cancer. Although, still is the paucity of reliable and repeatedly molecular methods to estimate
the predictive, genetic factors. Currently, the prolongation of overall survival of patients with NSCLC is
connected with both: new therapeutic agent synthesis as well as with predictive factors detection.
Onkol. Prak. Klin. 2010; 6, 2: 62-72
Onkol. Prak. Klin. 2010; 6, 2: 62-72
Keywords: non-smal cell lung cancerpredictive factorschemotherapyDNA repairβ-tubulinanueploidytyrosine kinase inhibitorsEGFR
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