Advance of theragnosis biomarkers in lung cancer: from clinical to molecular pathology and biology.

One distinct molecular subtype of non-small cell lung cancer (NSCLC) is defined by rearrangement of the anaplastic lymphoma kinase (ALK). The increasing knowledge over the last years has enabled the continuous improvement of ALK inhibitors; however, resistance in these patients remains a major concern. In this review, we summarize recent findings in ALK+-adenocarcinoma of the lung, highlighting the role of TP53 mutations in this specific cancer type and suggest new diagnostic strategies for the future, in order to improve patient's outcome.

[1]  Roman K. Thomas,et al.  Impact of TP53 mutation status on systemic treatment outcome in ALK-rearranged non-small-cell lung cancer , 2018, Annals of oncology : official journal of the European Society for Medical Oncology.

[2]  B. Besse,et al.  Making the first move in EGFR-driven or ALK-driven NSCLC: first-generation or next-generation TKI? , 2018, Nature Reviews Clinical Oncology.

[3]  J. Wolf,et al.  Genetic instability and recurrent MYC amplification in ALK‐translocated NSCLC: a central role of TP53 mutations , 2018, The Journal of pathology.

[4]  S. Gettinger,et al.  Safety and clinical activity results from a phase Ib study of alectinib plus atezolizumab in ALK+ advanced NSCLC (aNSCLC). , 2018 .

[5]  D. Spigel,et al.  Phase 1/2 Study of the Safety and Tolerability of Nivolumab Plus Crizotinib for the First‐Line Treatment of Anaplastic Lymphoma Kinase Translocation — Positive Advanced Non–Small Cell Lung Cancer (CheckMate 370) , 2018, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[6]  A. Iafrate,et al.  Impact of EML4-ALK Variant on Resistance Mechanisms and Clinical Outcomes in ALK-Positive Lung Cancer. , 2018, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  R. Rosell,et al.  Combination of immunotherapy with targeted therapies in advanced non-small cell lung cancer (NSCLC) , 2018, Therapeutic advances in medical oncology.

[8]  M. Kris,et al.  The Impact of Smoking and TP53 Mutations in Lung Adenocarcinoma Patients with Targetable Mutations—The Lung Cancer Mutation Consortium (LCMC2) , 2017, Clinical Cancer Research.

[9]  A. Shaw,et al.  Lorlatinib in ALK- or ROS1-rearranged non-small cell lung cancer: an international, multicenter, open-label phase 1 trial , 2017, The Lancet. Oncology.

[10]  P. Brousset,et al.  Detection of known and novel ALK fusion transcripts in lung cancer patients using next-generation sequencing approaches , 2017, Scientific Reports.

[11]  R. Bayliss,et al.  EML4-ALK Variants: Biological and Molecular Properties, and the Implications for Patients , 2017, Cancers.

[12]  Kentaro Inamura,et al.  Lung Cancer: Understanding Its Molecular Pathology and the 2015 WHO Classification , 2017, Front. Oncol..

[13]  A. Markham Brigatinib: First Global Approval , 2017, Drugs.

[14]  Rafal Dziadziuszko,et al.  Alectinib versus Crizotinib in Untreated ALK‐Positive Non–Small‐Cell Lung Cancer , 2017, The New England journal of medicine.

[15]  Md Abu Shufean,et al.  ALK: a tyrosine kinase target for cancer therapy , 2017, Cold Spring Harbor molecular case studies.

[16]  Lauren L. Ritterhouse,et al.  Molecular Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in ALK-Rearranged Lung Cancer. , 2016, Cancer discovery.

[17]  Shun Lu,et al.  Frequencies of ALK rearrangements in lung adenocarcinoma subtypes: a study of 2299 Chinese cases , 2016, SpringerPlus.

[18]  Philip J. Stephens,et al.  Total mutation burden (TMB) in lung cancer (LC) and relationship with response to PD-1/PD-L1 targeted therapies. , 2016 .

[19]  Y. Huang,et al.  Upregulation of PD-L1 by EML4-ALK fusion protein mediates the immune escape in ALK positive NSCLC: Implication for optional anti-PD-1/PD-L1 immune therapy for ALK-TKIs sensitive and resistant NSCLC patients , 2016, Oncoimmunology.

[20]  G. Tortora,et al.  Integrating the molecular background of targeted therapy and immunotherapy in lung cancer: a way to explore the impact of mutational landscape on tumor immunogenicity. , 2015, Translational lung cancer research.

[21]  V. Ganju,et al.  The Evolution of Therapies in Non-Small Cell Lung Cancer , 2015, Cancers.

[22]  A. Sokolenko,et al.  Novel ALK fusion partners in lung cancer. , 2015, Cancer letters.

[23]  R. Bayliss,et al.  Microtubule association of EML proteins and the EML4-ALK variant 3 oncoprotein require an N-terminal trimerization domain. , 2015, The Biochemical journal.

[24]  I. Lax,et al.  Heparin is an activating ligand of the orphan receptor tyrosine kinase ALK , 2015, Science Signaling.

[25]  William Pao,et al.  Rationale for co-targeting IGF-1R and ALK in ALK fusion positive lung cancer , 2014, Nature Medicine.

[26]  R. Patel,et al.  Induction of autophagy contributes to crizotinib resistance in ALK-positive lung cancer , 2014, Cancer biology & therapy.

[27]  A. Shaw,et al.  Current Status of Targeted Therapy for Anaplastic Lymphoma Kinase–Rearranged Non–Small Cell Lung Cancer , 2013, Clinical pharmacology and therapeutics.

[28]  Jae Cheol Lee,et al.  Epithelial‐mesenchymal transition leads to crizotinib resistance in H2228 lung cancer cells with EML4‐ALK translocation , 2013, Molecular oncology.

[29]  M. Ladanyi,et al.  ALK Rearrangements Are Mutually Exclusive with Mutations in EGFR or KRAS: An Analysis of 1,683 Patients with Non–Small Cell Lung Cancer , 2013, Clinical Cancer Research.

[30]  D De Ruysscher,et al.  Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. , 2012, Annals of oncology : official journal of the European Society for Medical Oncology.

[31]  R. Doebele,et al.  Treating ALK-positive lung cancer—early successes and future challenges , 2012, Nature Reviews Clinical Oncology.

[32]  A. Iafrate,et al.  Mechanisms of Acquired Crizotinib Resistance in ALK-Rearranged Lung Cancers , 2012, Science Translational Medicine.

[33]  Tatiana G. Kutateladze,et al.  Mechanisms of Resistance to Crizotinib in Patients with ALK Gene Rearranged Non–Small Cell Lung Cancer , 2012, Clinical Cancer Research.

[34]  Jeffrey W. Clark,et al.  Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. , 2010, The New England journal of medicine.

[35]  M. Boutterin,et al.  Activation of the orphan receptor tyrosine kinase ALK by zinc. , 2010, Biochemical and biophysical research communications.

[36]  Y. Ishikawa,et al.  EML4-ALK lung cancers are characterized by rare other mutations, a TTF-1 cell lineage, an acinar histology, and young onset , 2009, Modern Pathology.

[37]  H. Aburatani,et al.  Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer , 2007, Nature.

[38]  C. Powers,et al.  Midkine Binds to Anaplastic Lymphoma Kinase (ALK) and Acts as a Growth Factor for Different Cell Types* , 2002, The Journal of Biological Chemistry.

[39]  D. Wen,et al.  Identification of Anaplastic Lymphoma Kinase as a Receptor for the Growth Factor Pleiotrophin* , 2001, The Journal of Biological Chemistry.

[40]  T. Arakawa,et al.  Molecular characterization of ALK, a receptor tyrosine kinase expressed specifically in the nervous system , 1997, Oncogene.

[41]  A. Jemal,et al.  Cancer statistics, 2017 , 2017, CA: a cancer journal for clinicians.

[42]  C. Gridelli,et al.  Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. , 2012, Annals of oncology : official journal of the European Society for Medical Oncology.

[43]  J. Berman What is a Classification , 2012 .