open access

Vol 6, No 2 (2010)
Review paper
Published online: 2010-06-25
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Molecular factors in individualisation of chemiotherapy in non-small cell lung cancer - is it far future or close present?

Paweł Krawczyk, Janusz Milanowski
Onkol. Prak. Klin 2010;6(2):62-72.

open access

Vol 6, No 2 (2010)
REVIEW ARTICLES
Published online: 2010-06-25

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

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
Get Citation

Keywords

non-smal cell lung cancer; predictive factors; chemotherapy; DNA repair; β-tubulin; anueploidy; tyrosine kinase inhibitors; EGFR

About this article
Title

Molecular factors in individualisation of chemiotherapy in non-small cell lung cancer - is it far future or close present?

Journal

Oncology in Clinical Practice

Issue

Vol 6, No 2 (2010)

Article type

Review paper

Pages

62-72

Published online

2010-06-25

Bibliographic record

Onkol. Prak. Klin 2010;6(2):62-72.

Keywords

non-smal cell lung cancer
predictive factors
chemotherapy
DNA repair
β-tubulin
anueploidy
tyrosine kinase inhibitors
EGFR

Authors

Paweł Krawczyk
Janusz Milanowski

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