Clinical Trial: Chemoresistance and Involvement of the NOTCH Pathway in Patients With Lung Adenocarcinoma

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: CHEMO RESISTANCE TO PLATINUM COMPOUNDS AND NOTCH PATHWAYS IN PATIENTS RECEIVING NEOADJUVANT CHEMOTHRERAPY FOR LOCALLY ADVANCED ADENOCARCINOMA OF THE LUNG.

Brief Summary: Every year in France, 30.000 deaths are due to lung cancer and 39.500 new cases of this disease are diagnosed (INCa 2014). Patients suffering from locally advanced non-small-cell lung cancer (NSCLC), stage IIIa, usually undergo a multimodality treatment including chemotherapy with platinum compounds before surgery (called neoadjuvant chemotherapy or induction chemotherapy). The reason of this combined modality treatment is the really poor prognosis of patients presenting a disease already spread to lymph nodes (classified N2 when the lymph node under the carina is affected). Up till now, the five-year survival of patients who underwent surgical resection of N2 NSCLC does not exceed 15%

Detailed Summary:

Every year in France, 30.000 deaths are due to lung cancer and 39.500 new cases of this disease are diagnosed (INCa 2014). Patients suffering from locally advanced non-small-cell lung cancer (NSCLC), stage IIIa, usually undergo a multimodality treatment including chemotherapy with platinum compounds before surgery (called neoadjuvant chemotherapy or induction chemotherapy). The reason of this combined modality treatment is the really poor prognosis of patients presenting a disease already spread to lymph nodes (classified N2 when the lymph node under the carina is affected). Up till now, the five-year survival of patients who underwent surgical resection of N2 NSCLC does not exceed 15%.

NOTCH pathway seems to be implicated in the resistance of tumor to chemotherapy. It is known that NOTCH plays a role in the homeostasis of adult stem cells and of cancer stem cells, including intestine cancer and NSCLC. In breast cancer, it has been demonstrated that NOTCH 1 plays a role in the relapse and adding a treatment by an inhibitor of NOTCH decreases the recurrence rate. An activation of the NOTCH pathway was proven in human lung cancer cell lines (A549 and H460) treated with cisplatin. Furthermore, HES1 (Hairy enhance of split), a downstream gene resulting from NOTCH transcription, was upregulated in patient with relapse comparing resistant versus non-resistant adenocarcinoma NSCLC patients. It was proved, NOTCH pathway is associated with overall survival in NSCLC. Recently, it was showed that an inhibitor of NOTCH combined with chemotherapy strongly potentiates the anti-tumor effects of the systemic therapy. Therefore, one can hypothesize that platinum compound-induced NOTCH activation contributes to the resistance of NSCLC and beyond this point, to tumor progression.


Sponsor: University Hospital, Montpellier

Current Primary Outcome: analysed by immunochemistry (IHC) [ Time Frame: 1 day ]

The biopsies of lung tumour samples will be analysed by immunochemistry (IHC)


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • western blotting (WB) [ Time Frame: 1 day ]
    The biopsies of lung tumour samples will be analysed by western blotting (WB)
  • qPolymerase Chain Reaction (PCR) [ Time Frame: 1 day ]
    The biopsies of lung tumour samples will be analysed by qPolymerase Chain Reaction (PCR)


Original Secondary Outcome: Same as current

Information By: University Hospital, Montpellier

Dates:
Date Received: September 8, 2016
Date Started: September 2016
Date Completion: December 2017
Last Updated: September 8, 2016
Last Verified: August 2016