Retrospective Analysis of the Expression of the Neurotensin Receptor by Metastatic Lung Adenocarcinomas

Lung cancer is the leading cause of cancer mortality in France and worldwide. 60% of patients present themselves with a disease diagnosis immediately metastatic non curable. Adenocarcinomas account for 50% of incident tumors. Treatment is based on the platinum-based chemotherapy with or without maintenance therapy. When there is to exhaust this first line, a second line treatment is offered to the patient. Three drugs are allowed in this situation: docetaxel, erlotinib (inhibitor of the tyrosine kinase activity of the receptor for epidermal growth factor - TKI-EGFR) and pemetrexed (which in fact has become virtually standard in first online and in combination with platinum in all patients with non-squamous cancer, so that his place is in second line reduced facto). There is no recommendation for treatment in third line situation where only erlotinib is allowed.

Most recently, the nivolumab, anti-PD1 monoclonal antibody (which aims to enable immunutaire system) saw its demonstrated effectiveness in the second line and beyond in the two Phase 3 trials where it was compared with docetaxel for the treatment of squamous cell carcinoma and non-squamous. The very recent availability in France of the drug under an ATU fact that it will most likely become a standard second line, which will tend to place the third line docetaxel.

Therefore, erlotinib will be in 4th line situation. However, in the absence of an EGFR mutation (which is only seen in more than 10% of Caucasian patients) use of the drug does not seem appropriate or even harmful. A selection of patients likely to benefit from the prescription of EGFR TKI-is essential.

Neurotensin (NTS) is a polypeptide of 13 amino acids present and active in the central nervous system and the periphery. At the peripheral level, neurotensin is secreted postprandial by endocrine cells in the intestinal mucosa and is involved in the motor functions of the gastrointestinal tract. The effects of neurotensin pass through the activation of three subtypes of receptors which, mainly, NTSR1 and NTSR2 which are receptors coupled to G proteins in the extra-digestive normal tissues, including lung, torque NTS / NTSR1 n is not expressed physiologically. Rather, this complex is likely to recur in tumor tissues.

The mechanism of this effect is derogatory activation torque NTS / NTSR1 of matrix metalloproteinases which causes the release by the cell membrane ligands "EGF-like" and thus, activation of HER receptor (EGFR or HER1, HER2 and HER3). Indeed, in experimental tumors created by subcutaneous injection in athymic mouse cell lines adenocarcinomas NTS + / NTSR1 + (non-mutated EGFR), treatment with erlotinib - which blocks EGFR pathway - causes a significant decrease of tumor growth.

Expression of the neurotensin receptor in cancer cells metastatic primary bronchial adenocarcinoma is not known. Therefore, its pejorative prognostic value is not confirmed in the metastatic setting.