Beyond antiepidermal growth factor receptors and antiangiogenesis strategies for nonsmall cell lung cancer: Exploring a new frontier

Current Opinion in Oncology

Volumn 21, Issue 2, 2009, Pages 116-123

  Sangha, Randeep ^a,b   Lara Jr , Primo N ^a   Mack, Philip C ^a   Gandara, David R ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Epigenetics; Histone deacetylase inhibitors; Insulin like growth factor; New strategies; Nonsmall cell lung cancer; Personalized medicine; Targeted therapies

Indexed keywords

ANGIOGENESIS INHIBITOR; BEVACIZUMAB; CARBOPLATIN; CETUXIMAB; CISPLATIN; CP 751871; DOCETAXEL; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; ERLOTINIB; ETOPOSIDE; GEFITINIB; GEMCITABINE; HISTONE DEACETYLASE; HISTONE DEACETYLASE INHIBITOR; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY IMC A12; N (2 AMINOPHENYL) 4 (3 PYRIDINYLMETHOXYCARBONYLAMINOMETHYL)BENZAMIDE; NAVELBINE; PACLITAXEL; PANOBINOSTAT; PEMETREXED; PIVALOYLOXYMETHYL BUTYRATE; SNDX 275; SOMATOMEDIN C RECEPTOR; TAXANE DERIVATIVE; TROGLITAZONE; UNCLASSIFIED DRUG; VORINOSTAT;

CLINICAL TRIAL; DRUG EFFECT; DRUG EFFICACY; DRUG FATALITY; DRUG RESPONSE; ENZYME INHIBITION; EPIGENETICS; GENE SILENCING; HUMAN; LUNG NON SMALL CELL CANCER; LUNG SQUAMOUS CELL CARCINOMA; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; TRANSCRIPTION REGULATION; TUMOR SUPPRESSOR GENE;

ANGIOGENESIS INHIBITORS; ANTINEOPLASTIC AGENTS; CARCINOMA, NON-SMALL-CELL LUNG; CLINICAL TRIALS, PHASE II AS TOPIC; HISTONE DEACETYLASE INHIBITORS; HUMANS; LUNG NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; RECEPTOR, EPIDERMAL GROWTH FACTOR; RECEPTORS, SOMATOMEDIN; TUMOR MARKERS, BIOLOGICAL;

EID: 62349122171     PISSN: 10408746     EISSN: None     Source Type: Journal    
DOI: 10.1097/CCO.0b013e3283210489     Document Type: Review

References (57)

1. Jemal A, Siegel R, Ward E, et al. Cancer facts & figures 2008. Atlanta: American Cancer Society; 2008.
2. Winton T, Livingston R, Johnson D, et al. Vinorelbine plus cisplatin vs. observation in resected nonsmall-cell lung cancer. N Engl J Med 2005; 352:2589-2597.
3. Arriagada R, Bergman B, Dunant A, et al. Cisplatin-based adjuvant chemotherapy in patients with completely resected nonsmall-cell lung cancer. N Engl J Med 2004; 350:351-360.
4. Douillard JY, Rosell R, De Lena M, et al. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA nonsmall-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncol 2006; 7:719-727.
5. Pignon JP, Tribodet H, Scagliotti GV, et al. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol 2008; 26:3552-3559. This key Lung Adjuvant Cisplatin Evaluation (LACE) meta-analysis pooled data from five large trials of adjuvant cisplatin-based chemotherapy in completely resected NSCLC patients. The overall 5-year survival benefit was 5.2%, but benefit varied with stage of disease.
6. nd, Maddaus MA, et al. Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group and North Central Cancer Treatment Group Study Groups. J Clin Oncol, 2008; 26:5014-5017.
7. Zheng Z, Chen T, Li X, et al. DNA synthesis and repair genes RRM1 and ERCC1 in lung cancer. N Engl J Med 2007; 356:800-808. This article describes a novel methodology for quantitating ERCC1 and RRM1 expression using automated quantitative analysis (AQUA). Disease-free and overall survival was significantly associated with ERCC1 and RRM1 expression in early-stage (stage I) resected NSCLC.
8. Gautschi O, Mack PC, Davies AM, et al. Pharmacogenomic approaches to individualizing chemotherapy for nonsmall-cell lung cancer: current status and new directions. Clinical Lung Cancer 2008; 9:3129-3138. An excellent summary outlining the rationale and data for personalizing treatment in NSCLC using pharmacogenomic approaches.
9. Calhoun R, Jablons D, Lau D, et al. Adjuvant treatment of stage IB NSCLC: the problem of stage subset heterogeneity. Oncology (Williston Park) 2008; 22:511-516.
10. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al. Erlotinib in previously treated nonsmall-cell lung cancer. N Engl J Med 2005; 353:123-132.
11. Thatcher N, Chang A, Parikh P, et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced nonsmall-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet 2005; 366:1527-1537.
12. Kelly K, Chansky K, Caspar LE, et al. Phase III trial of maintenance gefitinib or placebo after concurrent chemoradiotherapy and docetaxel consolidation in inoperable stage III nonsmall-cell lung cancer: SWOG S0023. J Clin Oncol 2008; 26:2450-2456. This trial demonstrates inferior survival for patients treated with gefitinib maintenance after undergoing definitive cisplatin/etoposide chemoradiation and consolidation docetaxel for unresectable stage III NSCLC. On the basis of this study, routine use of EGFR-TKIs as maintenance therapy for stage III NSCLC should be avoided.
13. Mok T, Wu Y, Thongprasert S, et al. Phase III, randomised, open-label, first-line study of gefitinib vs carboplatin/paclitaxel in clinically selected patients with advanced nonsmall cell lung cancer. Ann Oncol 2008; 19 (supplement 8):LBA2. The Asian IPASS study is a randomized trial comparing first-line gefitinib versus carboplatin/paclitaxel in a clinically enriched population of never smokers or former smokers and adenocarcinoma histology. This trial demonstrated a significant PFS benefit for gefitinib and raises the possibility of treating select populations with EGFR TKIs as front-line therapy for advanced NSCLC.
14. Giaccone G, Herbst RS, Manegold C, et al. Gefitinib in combination with gemcitabine and cisplatin in advanced nonsmall-cell lung cancer: a phase III trial-INTACT 1. J Clin Oncol 2004; 22:777-784.
15. Herbst RS, Giaccone G, Schiller JH, et al. Gefitinib in combination with paclitaxel and carboplatin in advanced nonsmall-cell lung cancer: a phase III trial-INTACT 2. J Clin Oncol 2004; 22:785-794.
16. Herbst RS, Prager D, Hermann R, et al. TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced nonsmall-cell lung cancer. J Clin Oncol 2005; 23:5892-5899.
17. Gatzemeier U, Pluzanska A, Szczesna A, et al. Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced nonsmall-cell lung cancer: the Tarceva Lung Cancer Investigation Trial. J Clin Oncol 2007; 25:1545-1552. One of the four seminal articles that showed a lack of survival benefit for the combination of EGFR TKIs with platinum-based doublet chemotherapy in patients with chemotherapy-naive advanced NSCLC.
18. Mahaffey CM, Davies AM, Lara PN Jr, et al. Schedule-dependent apoptosis in K-ras mutant nonsmall-cell lung cancer cell lines treated with docetaxel and erlotinib: rationale for pharmacodynamic separation. Clin Lung Cancer 2007; 8:548-553. This preclinical study offers a hypothesis for the negative interaction of chemotherapy when given concurrently with EGFR TKIs. An intermittent dosing schedule of EGFR TKIs with chemotherapy was found to enhance cytotoxicity.
19. Pirker R, Szczesna A, von Pawel J, et al. FLEX: a randomized, multicenter, phase III study of cetuximab in combination with cisplatin/vinorelbine (CV) versus CV alone in the first-line treatment of patients with advanced nonsmall cell lung cancer (NSCLC). J Clin Oncol; 2008; ASCO Annual Meeting Proceedings 2008; 26:3 (Abstract).
20. Lynch TJ, Patel T, LD, et al. A randomized multicenter phase III study of cetuximab in combination with taxane/carboplatin versus taxane/carboplatin alone as first-line treatment for patients with advanced/metastatic nonsmall cell lung cancer. J Thorac Oncol 2007; 2:3340-3341 (Abstract B343-303).
21. ImClone. Erbitux phase III BMS-099 lung cancer study secondary endpoint update: overall survival results announced [press release]; 29 August 2008.
22. Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for nonsmall-cell lung cancer. N Engl J Med 2006; 355: 2542-2550.
23. Manegold C, von Pawel J, Zatloukal P, et al. Randomised, double-blind multicentre phase III study of bevacizumab in combination with cisplatin and gemcitabine in chemotherapy-naive patients with advanced or recurrent nonsquamous nonsmall cell lung cancer (NSCLC): BO17704. J Clin Oncol; 2007; ASCO Annual Meeting Proceedings 2007; 25:7514 (Abstract).
24. Manegold C, von Pawel J, Zatloukal P, et al. BO17704 (AVAIL): A phase III randomised study of first-line bevacizumab combined with cisplatin/gemcitabine in patients with advanced or recurrent nonsquamous, nonsmall cell lung cancer. Ann Oncol 2008; 19 (supplement 8):LBA1 q. This abstract presents the updated AVAiL data. A PFS benefit is seen but there remains no significant OS benefit.
25. Dziadziuszko R, Camidge DR, Hirsch FR. The insulin-like growth factor pathway in lung cancer. J Thorac Oncol 2008; 3:815-818. This short review summarizes the IGF pathway and its role in NSCLC tumorigenesis.
26. Ryan PD, Goss PE. The emerging role of the insulin-like growth factor pathway as a therapeutic target in cancer. Oncologist 2008; 13:16-24. A well written review article that explores the IGF pathway and the rationale for inhibiting this system as a therapeutic strategy.
27. Abuzzahab MJ, Schneider A, Goddard A, et al. IGF-1 receptor mutations resulting in intrauterine and postnatal growth retardation. N Engl J Med 2003; 349:2211-2222.
28. Samani AA, Yakar S, LeRoith D, et al. The role of the IGF system in cancer growth and metastasis: overview and recent insights. Endocr Rev 2007; 28:20-47.
29. Zhang X, Lin M, van Golen KL, et al. Multiple signaling pathways are activated during insulin-like growth factor-1 (IGF-1) stimulated breast cancer cell migration. Breast Cancer Res Treat 2005; 93:159-168.
30. Baserga R, Peruzzi F, Reiss K. The IGF-1 receptor in cancer biology. Int J Cancer 2003; 107:873-877.
31. Clemmons DR. Modifying IGF1 activity: an approach to treat endocrine disorders, atherosclerosis and cancer. Nat Rev Drug Discov 2007; 6:821-833.
32. Oh SH, Lee OH, Schroeder CP, et al. Antimetastatic activity of insulin-like growth factor binding protein-3 in lung cancer is mediated by insulin-like growth factor-independent urokinase-type plasminogen activator inhibition. Mol Cancer Ther 2006; 5:2685-2695.
33. Brown J, Delaine C, Zaccheo OJ, et al. Structure and functional analysis of the IGF-II/IGF2R interaction. EMBO J 2008; 27:265-276.
34. Minuto F, Del Monte P, Barreca A, et al. Evidence for an increased somatomedin-C/insulin-like growth factor I content in primary human lung tumors. Cancer Res 1986; 46:985-988.
35. Frankel SK, Moats-Staats BM, Cool CD, et al. Human insulin-like growth factor-1A expression in transgenic mice promotes adenomatous hyperplasia but not pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 2005; 288:L805-812.
36. Morgillo F, Woo JK, Kim ES, et al. Heterodimerization of insulin-like growth factor receptor/epidermal growth factor receptor and induction of survivin expression counteract the antitumor action of erlotinib. Cancer Res 2006; 66:10100-10111.
37. Chang YS, Kong G, Sun S, et al. Clinical significance of insulin-like growth factor-binding protein-3 expression in stage I nonsmall cell lung cancer. Clin Cancer Res 2002; 8:3796-3802.
38. Chang YS, Wang L, Liu D, et al. Correlation between insulin-like growth factor-binding protein-3 promoter methylation and prognosis of patients with stage I nonsmall cell lung cancer. Clin Cancer Res 2002; 8:3669-3675.
39. Chang YS, Wang L, Suh YA, et al. Mechanisms underlying lack of insulin-like growth factor-binding protein-3 expression in nonsmall-cell lung cancer. Oncogene 2004; 23:6569-6580.
40. Karp DD, LG P-A, Novello S, et al. High activity of the anti-IGF-IR antibody CP-751,871 in combination with paclitaxel and carboplatin in squamous NSCLC. J Clin Oncol, 2008 Annual Meeting Proceedings 2008; 26:8015 (Abstract).
41. Abe S, Funato T, Takahashi S, et al. Increased expression of insulin-like growth factor I is associated with Ara-C resistance in leukemia. Tohoku J Exp Med 2006; 209:217-228.
42. Allen GW, Saba C, Armstrong EA, et al. Insulin-like growth factor-I receptor sigaling blockade combined with radiation. Cancer Res 2007; 67:1155-1162. This study demonstrates that IMC-A12, an anti-IGF-1R monoclonal antibody, can enhance the effects of radiation therapy when given as an adjunct in preclinical models.
43. Desbois-Mouthon C, Cacheux W, Blivet-Van Eggelpoel MJ, et al. Impact of IGF-1R/EGFR cross-talks on hepatoma cell sensitivity to gefitinib. Int J Cancer 2006; 119:2557-2566.
44. Mulero-Navarro S, Esteller M. Epigenetic biomarkers for human cancer: the time is now. Crit Rev Oncol Hematol 2008; 68:1-11. A detailed review outlining epigenetic processes in the development of cancer. Clinical application of epigenetic markers and therapeutics aimed at favorably manipulating the epigenetic biology of cancer cells are discussed.
45. Gridelli C, Rossi A, Maione P. The potential role of histone deacetylase inhibitors in the treatment of nonsmall-cell lung cancer. Crit Rev Oncol Hematol 2008; 68:29-36. Histone deacetylase inhibitors are currently being explored in NSCLC and this article summarizes the mechanism of action, efficacy, and future development of these agents.
46. Bolden JE, Peart MJ, Johnstone RW. Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov 2006; 5:769-784.
47. Spange S, Wagner T, Heinzel T, et al. Acetylation of nonhistone proteins modulates cellular signalling at multiple levels. Int J Biochem Cell Biol (in press). Posttranslational acetylation of nonhistone proteins is relevant for tumorigenesis, cancer cell proliferation and immune functions. This review describes the role of histone deacetylase inhibitors in keeping key nonhistone proteins acetylated as a strategy to treat cancer.
48. Barlesi F, Giaccone G, Gallegos-Ruiz MI, et al. Global histone modifications predict prognosis of resected non small-cell lung cancer. J Clin Oncol 2007; 25:4358-4364. Using recursive partitioning analysis for 138 resected NSCLC tumor samples, this study showed that histone 3 lysine 4 dimethylation (H3K4diMe) as well as acetylation of histone 2A lysine 5 (H2AK5Ac) and histone 3 lysine 9 (H3K9Ac) influenced overall and disease-free survival for early-stage disease. The authors conclude that there is prognostic influence for epigenetic changes involving multiple histones and these changes may assist in selecting early-stage NSCLC patients for adjuvant therapy.
49. Cuneo KC, Fu A, Osusky K, et al. Histone deacetylase inhibitor NVP-LAQ824 sensitizes human nonsmall cell lung cancer to the cytotoxic effects of ionizing radiation. Anticancer Drugs 2007; 18:793-800.
50. Loprevite M, Tiseo M, Grossi F, et al. In vitro study of CI-994, a histone deacetylase inhibitor, in nonsmall cell lung cancer cell lines. Oncol Res 2005; 15:39-48.
51. Bissett D, O'Byrne KJ, von Pawel J, et al. Phase III study of matrix metalloproteinase inhibitor prinomastat in nonsmall-cell lung cancer. J Clin Oncol 2005; 23:842-849.
52. Ramalingam SS, Parise RA, Ramanathan RK, et al. Phase I and pharmacokinetic study of vorinostat, a histone deacetylase inhibitor, in combination with carboplatin and paclitaxel for advanced solid malignancies. Clin Cancer Res 2007; 13:3605-3610.
53. Edwards A, Li J, Atadja P, et al. Effect of the histone deacetylase inhibitor LBH589 against epidermal growth factor receptor-dependent human lung cancer cells. Mol Cancer Ther 2007; 6:2515-2524. This preclinical study demonstrates the ability of LBH589, a histone deacetylase inhibitor, to acetylate heat shock protein (HSP90) and to selectively trigger apoptosis in lung cancer cells with EGFR mutations. Interestingly, EGFR mutation status may be predictive of outcome with LBH589. Also, preclinical synergism between LBH589 and erlotinib is described, providing rationale for combining these agents in future studies.
54. Scagliotti GV, Parikh P, von Pawel J, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage nonsmall-cell lung cancer. J Clin Oncol 2008; 26:3543-3551. This large, randomized phase III trial demonstrates the noninferiority of cisplatin/pemetrexed to cisplatin/gemcitabine as first-line treatment for advanced NSCLC. Most importantly, after preplanned subset analysis, this trial showed survival differences based on histological subtype. This observation may have important consequences for personalizing treatments based on histology.
55. Sigmond J, Backus HH, Wouters D, et al. Induction of resistance to the multitargeted antifolate pemetrexed (ALIMTA) in WiDr human colon cancer cells is associated with thymidylate synthase overexpression. Biochem Pharmacol 2003; 66:431-438,
56. Giovannetti E, Mey V, Nannizzi S, et al. Cellular and pharmacogenetics foundation of synergistic interaction of pemetrexed and gemcitabine in human nonsmall-cell lung cancer cells. Mol Pharmacol 2005; 68:110-118.
57. Ceppi P, Volante M, Saviozzi S, et al. Squamous cell carcinoma of the lung compared with other histotypes shows higher messenger RNA and protein levels for thymidylate synthase. Cancer 2006; 107:1589-1596.