Lung Adenocarcinoma Clinical Trial
Official title:
CHEMO RESISTANCE TO PLATINUM COMPOUNDS AND NOTCH PATHWAYS IN PATIENTS RECEIVING NEOADJUVANT CHEMOTHRERAPY FOR LOCALLY ADVANCED ADENOCARCINOMA OF THE LUNG.
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%
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.
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Time Perspective: Retrospective
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