Oncogene addiction in non-small cell lung cancer: Focus on ROS1 inhibition.
Detection of molecular aberrations driving the biology and the clinical behavior of advanced non-small cell lung cancer (NSCLC) allows the adoption of specific therapeutic strategies dramatically impacting disease courses. Among these, ROS1 rearrangements are present in 1-2% of lung adenocarcinomas. Thanks to similarities between ALK and ROS1 oncogenes, lessons inferred from ALK can be applied to ROS1-positive NSCLC; nevertheless, disparities exist between diseases mastered by these two fusion genes. In the absence of more common genetic alterations detected in NSCLC (e.g. EGFR and KRAS mutations, ALK gene fusions), seeking for ROS1 rearrangements is crucial. Dedicated molecular diagnostics should be standardized, hopefully relying upon practical and efficient algorithms, comprehending immunohistochemistry and fluorescence in situ hybridisation. The major clinical impact exerted by crizotinib represents the main reason for which not even a sole ROS1-positive tumor should be undetected. The recent approval of the inhibitor by both American and European health agencies would hopefully boost the widespread testing for ROS1, eventually increasing the absolute number of positive cases, potential further source of information regarding molecular and clinical resistance. In vitro and clinical evidence have already been generated concerning crizotinib resistance and strategies to maintain patients under specific driver-inhibition are being successfully developed. Gathering data concerning diagnostics, preclinical evidence, clinical practice and ongoing studies, the present review depicts the current scenario of ROS1 inhibition in NSCLC.
INSERM, U981, Gustave Roussy Cancer Campus, Villejuif, France; Medical Oncology Unit, Univeristy Hospital of Parma, Italy. Electronic address: francescofacchinetti2@gmail.com.
Francesco
F
Facchinetti
Pathologic Anatomy Unit, Azienda USL Valle d'Aosta, Regional Hospital "Parini", Aosta, Italy. Electronic address: giurossi68@gmail.com.
Giulio
G
Rossi
Medical Oncology Unit, University of Verona, Verona, Italy. Electronic address: emilio.bria@univr.it.
Emilio
E
Bria
INSERM, U981, Gustave Roussy Cancer Campus, Villejuif, France; Drug Development Department (DITEP), Gustave Roussy Cancer Campus, Villejuif, France; University Paris-Sud, Kremlin Bicetre/Chatenay-Malabry, France. Electronic address: Jean-Charles.Soria@gustaveroussy.fr.
Jean-Charles
JC
Soria
University Paris-Sud, Kremlin Bicetre/Chatenay-Malabry, France; Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France. Electronic address: Benjamin.Besse@gustaveroussy.fr.
Benjamin
B
Besse
Medical Oncology Unit, Univeristy Hospital of Parma, Italy. Electronic address: rominari@ao.pr.it.
Roberta
R
Minari
INSERM, U981, Gustave Roussy Cancer Campus, Villejuif, France. Electronic address: luc.friboulet@gustaveroussy.fr.
Luc
L
Friboulet
Medical Oncology Unit, Univeristy Hospital of Parma, Italy. Electronic address: mtiseo@ao.pr.it.
Marcello
M
Tiseo
D000631:Aminopyridines; D000813:Anilides / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics*; D000077547:Crizotinib; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015321:Gene Rearrangement; D006801:Humans; D007191:Indazoles / Q000627:therapeutic use; D007769:Lactams; D047029:Lactams, Macrocyclic / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D025202:Molecular Diagnostic Techniques; D050596:Oncogene Fusion; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011720:Pyrazoles / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use; D013450:Sulfones / Q000627:therapeutic use
D000631:Aminopyridines; D000813:Anilides; D000970:Antineoplastic Agents; D001549:Benzamides; D007191:Indazoles; D007769:Lactams; D047029:Lactams, Macrocyclic; D011518:Proto-Oncogene Proteins; D011720:Pyrazoles; D011725:Pyridines; D011743:Pyrimidines; D013450:Sulfones; C558660:cabozantinib; D000077547:Crizotinib; D011505:Protein-Tyrosine Kinases; C062333:ROS1 protein, human; C586847:ceritinib; C000607349:entrectinib; C000590786:lorlatinib
ALK gene fusion; Crizotinib; Non-small cell lung cancer; Novel-generation inhibitors; ROS1 rearrangement; Resistance