Prolonged survival after neoadjuvant chemotherapy related with specific molecular alterations in the patients with nonsmall-cell lung carcinoma

Exp Mol Pathol. 2015 Feb;98(1):27-32. doi: 10.1016/j.yexmp.2014.11.010. Epub 2014 Nov 20.

Abstract

Lung cancer is the most common cause of neoplasia-related death worldwide. Accounting for approximately 80% of all lung carcinomas, the non-small cell lung carcinoma (NSCLC) is the most common clinical form with its two predominant histological types, adenocarcinoma (ADC) and squamous cell carcinoma (SCC). Although surgical resection is the most favorable treatment for patients with NSCLC, relapse is still high, so neoadjuvant chemotherapy (NAC) is an accepted treatment modality. In this study we examined whether some of the key molecules associated with the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR signaling pathways could have predictive and prognostic value for the NAC application. To that end we examined the expression status of PTEN, pAKT, pERK and loss of heterozygosity (LOH) of PTEN in two groups of NSCLC patients, those who received and those who did not receive NAC. LOH PTEN and low pERK expression is shown to be correlated with the longest survival of patients with SCC and ADC, respectively, who received NAC. These results point that the application of NAC is beneficial in the NSCLC patients with specific molecular alterations which could further help to improve constant search for the druggable molecular targets used in personalized therapy.

Keywords: Neodjuvant chemotherapy; Non-small cell lung carcinoma; PTEN; pAKT; pERK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality*
  • Adenocarcinoma / pathology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / mortality*
  • Carcinoma, Squamous Cell / pathology
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunoenzyme Techniques
  • Loss of Heterozygosity
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoadjuvant Therapy*
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • PTEN Phosphohydrolase / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Polymerase Chain Reaction
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Survival Rate
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Biomarkers, Tumor
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • PTEN Phosphohydrolase
  • PTEN protein, human