Pharmacogenomics of Cisplatin Sensitivity in Non-small Cell Lung Cancer

Cisplatin, a platinum-based chemotherapeutic drug, has been used for over 30 years in a wide variety of cancers with varying degrees of success. In particular, cisplatin has been used to treat late stage non-small cell lung cancer (NSCLC) as the standard of care. However, therapeutic outcomes vary from patient to patient. Considerable efforts have been invested to identify biomarkers that can be used to predict cisplatin sensitivity in NSCLC. Here we reviewed current evidence for cisplatin sensitivity biomarkers in NSCLC. We focused on several key pathways, including nucleotide excision repair, drug transport and metabolism. Both expression and germline DNA variation were evaluated in these key pathways. Current evidence suggests that cisplatin-based treatment could be improved by the use of these biomarkers.

[1]  C. Manegold Non-small Cell Lung Cancer Treatment , 2007 .

[2]  Teruhiko Yoshida,et al.  Genetic polymorphisms of copper- and platinum drug-efflux transporters ATP7A and ATP7B in Japanese cancer patients. , 2009, Drug Metabolism and Pharmacokinetics.

[3]  G. Scagliotti,et al.  Nucleotide excision repair pathways involved in Cisplatin resistance in non-small-cell lung cancer. , 2003, Cancer control : journal of the Moffitt Cancer Center.

[4]  J. Zisowsky,et al.  Relevance of drug uptake and efflux for cisplatin sensitivity of tumor cells. , 2007, Biochemical pharmacology.

[5]  S. Assinder,et al.  The mammalian copper transporters CTR1 and CTR2 and their roles in development and disease. , 2013, The international journal of biochemistry & cell biology.

[6]  Hai-Bo Wei,et al.  A meta-analytic review of ERCC1/MDR1 polymorphism and chemosensitivity to platinum in patients with advanced non-small cell lung cancer. , 2012, Chinese medical journal.

[7]  Honghao Zhou,et al.  Genetic polymorphism of copper transporter protein 1 is related to platinum resistance in Chinese non‐small cell lung carcinoma patients , 2012, Clinical and experimental pharmacology & physiology.

[8]  M. Gottesman,et al.  The role of cellular accumulation in determining sensitivity to platinum-based chemotherapy. , 2008, Annual review of pharmacology and toxicology.

[9]  Liqiang Song,et al.  miR‐495 Enhances the Sensitivity of Non‐Small Cell Lung Cancer Cells to Platinum by Modulation of Copper‐Transporting P‐type Adenosine Triphosphatase A (ATP7A) , 2014, Journal of cellular biochemistry.

[10]  U. Jaehde,et al.  Relevance of copper transporter 1 for cisplatin resistance in human ovarian carcinoma cells. , 2012, Journal of inorganic biochemistry.

[11]  Elisabeth Brambilla,et al.  DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. , 2006, The New England journal of medicine.

[12]  Y. Kashiki,et al.  Immunohistochemical expression of glutathione transferase-pi in untreated primary non-small-cell lung cancer. , 2000, Cancer detection and prevention.

[13]  Yanlong Yang,et al.  The association between the GSTP1 A313G and GSTM1 null/present polymorphisms and the treatment response of the platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients: a meta-analysis , 2014, Tumor Biology.

[14]  B. Blair,et al.  The Role of the Mammalian Copper Transporter 1 in the Cellular Accumulation of Platinum-Based Drugs , 2009, Molecular Pharmacology.

[15]  J. Kaplan,et al.  A Re-Evaluation of the Role of hCTR1, the Human High-Affinity Copper Transporter, in Platinum-Drug Entry into Human Cells , 2013, Molecular Pharmacology.

[16]  P. Drew,et al.  The proteomic analysis of cisplatin resistance in breast cancer cells. , 2007, Oncology research.

[17]  D. Cescon,et al.  Pharmacogenetic and Germline Prognostic Markers of Lung Cancer , 2011, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[18]  S. Lippard,et al.  HMG-domain proteins specifically inhibit the repair of the major DNA adduct of the anticancer drug cisplatin by human excision nuclease. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Jun Liang,et al.  Genetic polymorphisms of GSTP1 and XRCC1: prediction of clinical outcome of platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC) patients. , 2011, Swiss medical weekly.

[20]  H. Groen,et al.  ERCC1, hRad51, and BRCA1 protein expression in relation to tumour response and survival of stage III/IV NSCLC patients treated with chemotherapy. , 2005, Lung cancer.

[21]  I. Wistuba,et al.  Tissue platinum concentration and tumor response in non-small-cell lung cancer. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  H. Kato,et al.  Identification of postoperative adjuvant chemotherapy responders in non‐small cell lung cancer by novel biomarker , 2005, International journal of cancer.

[23]  S. Howell,et al.  Cellular accumulation of the anticancer agent cisplatin: a review. , 1993, British Journal of Cancer.

[24]  Dianke Yu,et al.  Pharmacogenetic role of ERCC1 genetic variants in treatment response of platinum-based chemotherapy among advanced non-small cell lung cancer patients , 2012, Tumor Biology.

[25]  J. Pignon,et al.  ERCC1 isoform expression and DNA repair in non-small-cell lung cancer. , 2013, The New England journal of medicine.

[26]  U. G. Dailey Cancer,Facts and Figures about. , 2022, Journal of the National Medical Association.

[27]  R. Rosell,et al.  DNA repair and cisplatin resistance in non-small-cell lung cancer. , 2002, Lung cancer.

[28]  Penny A. Johnson,et al.  Resistance gene expression determines the in vitro chemosensitivity of non-small cell lung cancer (NSCLC) , 2009, BMC Cancer.

[29]  S. Anttila,et al.  Immunohistochemical localization of glutathione S-transferases in human lung. , 1993, Cancer research.

[30]  Joe Y. Chang,et al.  Germline genetic variations in drug action pathways predict clinical outcomes in advanced lung cancer treated with platinum-based chemotherapy , 2008, Pharmacogenetics and genomics.

[31]  Zhaoqian Liu,et al.  Meta-Analysis on Pharmacogenetics of Platinum-Based Chemotherapy in Non Small Cell Lung Cancer (NSCLC) Patients , 2012, PloS one.

[32]  J. Yu,et al.  Messenger RNA levels of XPAC and ERCC1 in ovarian cancer tissue correlate with response to platinum-based chemotherapy. , 1994, The Journal of clinical investigation.

[33]  S. Howell,et al.  Contribution of the Major Copper Influx Transporter CTR1 to the Cellular Accumulation of Cisplatin, Carboplatin, and Oxaliplatin , 2006, Molecular Pharmacology.

[34]  G. Bepler,et al.  Transcripts in pretreatment biopsies from a three-arm randomized trial in metastatic non-small-cell lung cancer , 2003, Oncogene.

[35]  D. Bernstein,et al.  Ethnic distribution of the glutathione transferase Mu 1-1 (GSTM1) null genotype in 1473 individuals and application to bladder cancer susceptibility. , 1994, Carcinogenesis.

[36]  D. Kavanagh,et al.  Is overexpression of HER-2 a predictor of prognosis in colorectal cancer? , 2009, BMC Cancer.

[37]  R. Ueda,et al.  Glutathione S-transferase pi levels in a panel of lung cancer cell lines and its relation to chemo-radiosensitivity. , 1993, Japanese journal of clinical oncology.

[38]  S. Howell,et al.  Copper transporters regulate the cellular pharmacology and sensitivity to Pt drugs. , 2005, Critical reviews in oncology/hematology.

[39]  Yu-Hsuan Lai,et al.  Predictive and prognostic value of human copper transporter 1 (hCtr1) in patients with stage III non-small-cell lung cancer receiving first-line platinum-based doublet chemotherapy. , 2012, Lung cancer.

[40]  S. Islam,et al.  Commercial laboratory testing of excision repair cross-complementation group 1 expression in non-small cell lung cancer. , 2014, The oncologist.

[41]  G. Samimi,et al.  Increased Expression of the Copper Efflux Transporter ATP7A Mediates Resistance to Cisplatin, Carboplatin, and Oxaliplatin in Ovarian Cancer Cells , 2004, Clinical Cancer Research.

[42]  S. Howell,et al.  The copper transporter CTR1 regulates cisplatin uptake in Saccharomyces cerevisiae. , 2002, Molecular pharmacology.

[43]  J. Rommens,et al.  The Wilson disease gene is a putative copper transporting P–type ATPase similar to the Menkes gene , 1993, Nature Genetics.

[44]  Joe Y. Chang,et al.  Association between glutathione S‐transferase π polymorphisms and survival in patients with advanced nonsmall cell lung carcinoma , 2006, Cancer.

[45]  U. Gonlugur,et al.  The Association Between Polymorphisms in Glutathione S-Transferase (GSTM1 and GSTT1) and Lung Cancer Outcome , 2006, Cancer investigation.

[46]  A. Townsend,et al.  Role of glutathione S-transferase P1-1 in the cellular detoxification of cisplatin , 2008, Molecular Cancer Therapeutics.

[47]  Hong-yan Cheng,et al.  MRP2 and GSTP1 polymorphisms and chemotherapy response in advanced non-small cell lung cancer , 2009, Cancer Chemotherapy and Pharmacology.

[48]  T. Triche,et al.  An immunohistochemical study of pi class glutathione S-transferase expression in normal human tissue. , 1990, The American journal of pathology.

[49]  P. McHugh,et al.  Defects in interstrand cross-link uncoupling do not account for the extreme sensitivity of ERCC1 and XPF cells to cisplatin. , 2002, Nucleic acids research.

[50]  Yu-hong Li,et al.  Copper-transporting P-type adenosine triphosphatase (ATP7A) is associated with platinum-resistance in non-small cell lung cancer (NSCLC) , 2012, Journal of Translational Medicine.

[51]  Z. Siddik,et al.  Role of human copper transporter Ctr1 in the transport of platinum-based antitumor agents in cisplatin-sensitive and cisplatin-resistant cells. , 2004, Molecular cancer therapeutics.

[52]  K. Valerie,et al.  A truncated human xeroderma pigmentosum complementation group A protein expressed from an adenovirus sensitizes human tumor cells to ultraviolet light and cisplatin. , 2001, Cancer research.

[53]  R. Booton,et al.  ERCC1 mRNA Expression Is Not Associated with Response and Survival after Platinum-Based Chemotherapy Regimens in Advanced Non-Small Cell Lung Cancer , 2007, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[54]  Wen‐Shan Li,et al.  Inhibition of glutathione S-transferase M1 by new gabosine analogues is essential for overcoming cisplatin resistance in lung cancer cells. , 2011, Journal of medicinal chemistry.

[55]  Yi Shi,et al.  Predictive value of ERCC1 and XPD polymorphism in patients with advanced non-small cell lung cancer receiving platinum-based chemotherapy: a systematic review and meta-analysis , 2011, Medical oncology.

[56]  D. Gandara,et al.  Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[57]  T. Vaughan,et al.  Glutathione S-transferase M1, T1, and P1 polymorphisms and survival among lung cancer patients. , 2003, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[58]  Shunqing Xu,et al.  Sensitization to the cytotoxicity of cisplatin by transfection with nucleotide excision repair gene xeroderma pigmentosun group A antisense RNA in human lung adenocarcinoma cells. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[59]  James Allan,et al.  Polymorphism in glutathione S-transferase P1 is associated with susceptibility to chemotherapy-induced leukemia , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[60]  J. Yokota,et al.  LEVELS OF GLUTATHIONES TRANSFERASE π mRNA IN HUMAN LUNG CANCER CELL LINES CORRELATE WITH THE RESISTANCE TO CISPLATIN AND CARBOPLATIN , 1988, Japanese journal of cancer research : Gann.

[61]  Y. Maehara,et al.  Combined evaluation of Rad51 and ERCC1 expressions for sensitivity to platinum agents in non‐small cell lung cancer , 2007, International journal of cancer.

[62]  K. Ogawa,et al.  Prognostic Value of the Cu-Transporting ATPase in Ovarian Carcinoma Patients Receiving Cisplatin-Based Chemotherapy , 2004, Clinical Cancer Research.

[63]  Bing Zhou,et al.  hCTR1: a human gene for copper uptake identified by complementation in yeast. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[64]  Laura Smith,et al.  Expression microarray analysis reveals genes associated with in vitro resistance to cisplatin in a cell line model , 2007, Acta oncologica.

[65]  Baorui Liu,et al.  ERCC1 and BRCA1 mRNA expression levels in metastatic malignant effusions is associated with chemosensitivity to cisplatin and/or docetaxel , 2008, BMC Cancer.

[66]  K. Tew Glutathione-Associated Enzymes In Anticancer Drug Resistance. , 2016, Cancer research.

[67]  S. Belinsky,et al.  HIF1α regulated expression of XPA contributes to cisplatin resistance in lung cancer. , 2012, Carcinogenesis.

[68]  G. B. Smith,et al.  Human glutathione S-transferase P1 polymorphisms: relationship to lung tissue enzyme activity and population frequency distribution. , 1998, Carcinogenesis.

[69]  B. Blair,et al.  The role of the N-terminus of mammalian copper transporter 1 in the cellular accumulation of cisplatin. , 2010, Biochemical pharmacology.

[70]  Abida Haque,et al.  Expression of glutathione S-transferase pi and glutathione synthase correlates with survival in early stage non-small cell carcinomas of the lung. , 2007, Human pathology.

[71]  T. Ishikawa,et al.  The roles of copper transporters in cisplatin resistance , 2007, Cancer and Metastasis Reviews.

[72]  Hong-yan Cheng,et al.  Polymorphisms in XPD Gene Could Predict Clinical Outcome of Platinum-Based Chemotherapy for Non-Small Cell Lung Cancer Patients: A Meta-Analysis of 24 Studies , 2013, PloS one.

[73]  K. Kohno,et al.  Increased expression of glutathione S-transferase gene in cis-diamminedichloroplatinum(II)-resistant variants of a Chinese hamster ovary cell line. , 1989, Cancer research.

[74]  S. Howell,et al.  Copper transporter 2 regulates intracellular copper and sensitivity to cisplatin. , 2014, Metallomics : integrated biometal science.

[75]  M. Mutoh,et al.  Copper-transporting P-type adenosine triphosphatase (ATP7B) is associated with cisplatin resistance. , 2000, Cancer research.

[76]  N. Dubrawsky Cancer statistics , 1989, CA: a cancer journal for clinicians.

[77]  V. B. Konkimalla,et al.  Role of transporter genes in cisplatin resistance. , 2008, In vivo.

[78]  Jian Gu,et al.  Pharmacogenomics of platinum-based chemotherapy in NSCLC , 2009, Expert opinion on drug metabolism & toxicology.

[79]  S. Packman,et al.  Isolation of a candidate gene for Menkes disease and evidence that it encodes a copper–transporting ATPase , 1993, Nature Genetics.

[80]  T. Ward,et al.  Glutathione-S-Transferase P1 Isoenzyme Polymorphisms, Platinum-Based Chemotherapy, and Non-small Cell Lung Cancer , 2006, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[81]  H. Guchelaar,et al.  Pharmacogenetics of Cancer and DNA Repair Enzymes , 2011 .

[82]  D. Alberts,et al.  Increase in expression of the copper transporter ATP7A during platinum drug-based treatment is associated with poor survival in ovarian cancer patients. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[83]  I. Herskowitz,et al.  Uptake of the anticancer drug cisplatin mediated by the copper transporter Ctr1 in yeast and mammals , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[84]  D. Schaid,et al.  Glutathione Pathway Genetic Polymorphisms and Lung Cancer Survival After Platinum-Based Chemotherapy , 2010, Cancer Epidemiology, Biomarkers & Prevention.

[85]  B. Blair,et al.  Copper Transporter 2 Regulates the Cellular Accumulation and Cytotoxicity of Cisplatin and Carboplatin , 2009, Clinical Cancer Research.

[86]  H. Suemizu,et al.  ATP7B expression is associated with in vitro sensitivity to cisplatin in non-small cell lung cancer. , 2010, Oncology letters.

[87]  R. Kurzrock,et al.  Overcoming Platinum Resistance through the Use of a Copper-Lowering Agent , 2012, Molecular Cancer Therapeutics.

[88]  K. Cowan,et al.  Expression of human mu or alpha class glutathione S-transferases in stably transfected human MCF-7 breast cancer cells: effect on cellular sensitivity to cytotoxic agents. , 1992, Molecular pharmacology.

[89]  A. Jemal,et al.  Cancer statistics, 2014 , 2014, CA: a cancer journal for clinicians.

[90]  E. Gamazon,et al.  Genome-wide Meta-analysis Identifies Variants Associated with Platinating Agent Susceptibility Across Populations , 2011, The Pharmacogenomics Journal.

[91]  D. Stewart Tumor and host factors that may limit efficacy of chemotherapy in non-small cell and small cell lung cancer. , 2010, Critical reviews in oncology/hematology.

[92]  D. Gandara,et al.  Customizing cisplatin based on quantitative excision repair cross-complementing 1 mRNA expression: a phase III trial in non-small-cell lung cancer. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[93]  J. Essigmann,et al.  Mechanisms of resistance to cisplatin. , 2001, Mutation research.

[94]  D. Thiele,et al.  The role of Ctr1 and Ctr2 in mammalian copper homeostasis and platinum-based chemotherapy. , 2015, Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements.

[95]  J. Hayes,et al.  The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. , 1995, Critical reviews in biochemistry and molecular biology.

[96]  Y. Pommier,et al.  Transcription-coupled nucleotide excision repair as a determinant of cisplatin sensitivity of human cells. , 2002, Cancer research.

[97]  J. Hayes,et al.  Glutathione S-Transferase Polymorphisms and Their Biological Consequences , 2000, Pharmacology.

[98]  H. Suemizu,et al.  Expression of copper-transporting P-type adenosine triphosphatase (ATP7B) correlates with cisplatin resistance in human non-small cell lung cancer xenografts. , 1994 .

[99]  D. Hanahan,et al.  Enhancing tumor-specific uptake of the anticancer drug cisplatin with a copper chelator. , 2010, Cancer cell.

[100]  P. Lohman,et al.  Adducts of the antitumor drug cis-diamminedichloroplatinum(II) with DNA: formation, identification, and quantitation. , 1985, Biochemistry.

[101]  M. Dolan,et al.  Molecular mechanisms of resistance and toxicity associated with platinating agents. , 2007, Cancer treatment reviews.