Radioresistance of Non-Small Cell Lung Cancers and Therapeutic Perspectives

Mathieu Césaire (1, 2) , Juliette Montanari (2) , Hubert Curcio (1) , Delphine Lerouge (1) , Radj Gervais (1) , Pierre Demontrond (1) , Jacques Balosso (1) , François Chevalier (2)

1 UNICANCER/CRLC - Centre Régional de Lutte contre le Cancer François Baclesse [Caen]
2 ARIA - Accueil et Recherche en Radiobiologie des Ions Accélérés

Survival in unresectable locally advanced stage non-small cell lung cancer (NSCLC) patients remains poor despite chemoradiotherapy. Recently, adjuvant immunotherapy improved survival for these patients but we are still far from curing most of the patients with only a 57% survival remaining at 3 years. This poor survival is due to the resistance to chemoradiotherapy, local relapses, and distant relapses. Several biological mechanisms have been found to be involved in the chemoradioresistance such as cancer stem cells, cancer mutation status, or the immune system. New drugs to overcome this radioresistance in NSCLCs have been investigated such as radiosensitizer treatments or immunotherapies. Different modalities of radiotherapy have also been investigated to improve efficacity such as dose escalation or proton irradiations. In this review, we focused on biological mechanisms such as the cancer stem cells, the cancer mutations, the antitumor immune response in the first part, then we explored some strategies to overcome this radioresistance in stage III NSCLCs with new drugs or radiotherapy modalities.

Mots clés: non-small-cell lung cancer; cancer stem cell; cancer mutation; radiotherapy; immunotherapy; proton irradiation

Domaines: Cancer; Pneumologie et système respiratoire; Médecine nucléaire; Immunothérapie

Mathieu Césaire, Juliette Montanari, Hubert Curcio, Delphine Lerouge, Radj Gervais, et al.. Radioresistance of Non-Small Cell Lung Cancers and Therapeutic Perspectives. Cancers, 2022, 14 (12), pp.2829. ⟨10.3390/cancers14122829⟩. ⟨hal-03697588⟩