Skip to main content

Chemoprevention of Lung Cancer: New Directions

  • Conference paper
Tumor Prevention and Genetics

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 163))

Abstract

The refractoriness of advanced lung cancer to current treatment modalities requires new approaches to reduce the public health burden associated with this disease. One strategy that is currently being tested is chemoprevention, which aims to prevent the development of cancer in populations that are at high risk for cancer due to a variety of genetic or environmental factors. The key to the success of this approach, however, requires the identification of appropriately targeted efficacious, non-toxic agents as well as the methodologies to efficiently test them. Given the lack of success of previous phase III definitive lung cancer chemoprevention trials, there is a need for smaller scale phase II trials with molecular, imaging, or histologic endpoints to demonstrate preliminary safety and efficacy. The identification of molecular pathways critical to lung carcinogenesis offers the opportunity to develop targeted therapies for prevention. Means of optimizing the risk/benefit ratio associated with treatment include regional drug delivery that minimizes systemic toxicities and combination therapies. Identification of the most appropriate cohorts, such as former smokers without ongoing DNA damage due to carcinogen exposure, may uncover benefits that are hidden in a mixed population. Equally important is the identification of appropriate study endpoints that are predictive of patient outcomes such as cancer incidence. Further understanding of lung cancer biology will be critical to the success of future clinical trials.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Achiwa H, Yatabe Y, Hida T, et al (1999) Prognostic significance of elevated cyclooxygenase 2 expression in primary, resected lung adenocarcinomas. Clin Cancer Res 5:1001–1005

    PubMed  CAS  Google Scholar 

  • Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. (1994) The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Eng J Med 330:1029–1035

    Article  Google Scholar 

  • Arnold AM, Browman GP, Levine MN, et al (1992) The effect of the synthetic retinoid etretinate on sputum cytology: results from a randomised trial. Br J Cancer 65:737–743

    Article  PubMed  CAS  Google Scholar 

  • Avis IM, Jett M, Boyle T, et al (1996) Growth control of lung cancer by interruption of 5-lipoxygenase-mediated growth factor signaling. J Clin Invest 97:806–813

    Article  PubMed  CAS  Google Scholar 

  • Carbone DP (1997) The biology of lung cancer. Semin Oncol 24:388–401

    PubMed  CAS  Google Scholar 

  • Castonguay A, Rioux N, Duperron C, et al (1998) Inhibition of lung tumorigenesis by NSAIDs:A working hypothesis. Exp Cell Res 24:605–615. 1998

    CAS  Google Scholar 

  • Clark LC, Combs GF, Turnbull BW, et al (1996) Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. JAMA 276:1957–1963

    Article  PubMed  CAS  Google Scholar 

  • Druker BJ, Talpaz M, Resta D, et al (2001) Efficacy and safety of a specific inhibitor of the Bcr-Abl tyrosine kinase in chronic myeloid leukemia. N Eng J Med 344:1031–1037

    Article  CAS  Google Scholar 

  • Estensen RD and Wattenberg LW. (1993) Studies of chemopreventive effects of myo-inositol on benzo[a]-pyrene-induced neoplasia of the lung and forestomach of female AlJ mice. Carcinogenesis (Lond) 14:1975–1977

    Article  CAS  Google Scholar 

  • Fisher B, Costantino JP, Wickerham DL, et al (1998) Tamoxifen for prevention of breast cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-l Study. J Natl Cancer Inst 90:1371–1388

    Article  PubMed  CAS  Google Scholar 

  • Greenlee RT, Hill-Harmon MB, Murray T, et al (2001) Cancer statistics 2001. CA Cancer J Clin 51:15–36

    Article  PubMed  CAS  Google Scholar 

  • Hida T, Yatabe Y, Achiwa H, et al (1998) Increased expression of cyclooxygenase 2 occurs frequently in human lung cancers, specifically in adenocarcinomas. Cancer Res 58:3761–3764

    PubMed  CAS  Google Scholar 

  • Hong WK, Endicott J, Itri LM, et al (1986) 13-cis-retinoic acid in the treatment of oral leukoplakia. N Eng J Med 315:1501–1505

    Article  CAS  Google Scholar 

  • Hong WK, Lippman SM, Itri LM, et al (1990) Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N Eng J Med 323:795–801

    Article  CAS  Google Scholar 

  • Khuri FR, Wu H, Lee N, et al (2001) Cyclooxygenase-2 overexpression is a marker of poor prognosis in stage I non-small cell lung cancer. Clin Cancer Res 7:861–867

    PubMed  CAS  Google Scholar 

  • Kurie JM, Lee JS, Khuri FR, et al (2000) N-(4-hydroxyphenyl)retinamide in the chemoprevention of squamous metaplasia and dysplasia of the bronchial epithelium. Clin Cancer Res 5:2973–2979

    Google Scholar 

  • Kurie JM, Shin HJ, Lee JS, et al (1996) Increased epidermal growth factor receptor expression in metaplastic bronchial epithelium. Clin Cancer Res 2:1787–1793

    PubMed  CAS  Google Scholar 

  • Lee JS, Lippman SM, Benner SE, et al (1994) Randomized placebo-controlled trial of isotretinoin in chemoprevention of bronchial squamous metaplasia. J Clin OncoI 12:937–945

    CAS  Google Scholar 

  • Lippman SM, Batsakis JG, Toth BB, et al (1993) Comparison of low-dose isotretinoin with beta carotene to prevent oral carcinogenesis. N Eng J Med 328:15–20

    Article  CAS  Google Scholar 

  • Lippman SM, Benner SE, Hong WK. (1994) Cancer chemoprevention. J Clin Oncol 12:851–873

    PubMed  CAS  Google Scholar 

  • Lippman SM, Leen, Karp DD, et al (2001) Randomized phase III Intergroup trial of isotretinoin to prevent second primary tumors in stage I non-small-cell lung cancer. J Natl Cancer Inst 93:605–618

    Article  PubMed  CAS  Google Scholar 

  • Lippman SM, Lee JS, Lotan R, et al (1990) Biomarkers as intermediate end points in chemoprevention trials. J Natl Cancer Inst 82:555–560

    Article  PubMed  CAS  Google Scholar 

  • Lippman SM, Spitz MR (2001) Lung cancer chemoprevention: an integrated approach J Clin Oncol 19:74s–82s

    PubMed  CAS  Google Scholar 

  • Mao L, Lee JS, Kurie JM, et al (1997) Clonal genetic alterations in the lungs of current and former smokers. J Natl Cancer Inst 89:857–862

    Article  PubMed  CAS  Google Scholar 

  • McLarty JW, Holiday DB, Girard, WM, et al (1995), β-carotene, vitamin A, and lung cancer chemoprevention: results of an intermediate endpoint study. Am J Clin Nutr 62:1431s–1438s

    PubMed  CAS  Google Scholar 

  • Moody TR, Leyton J, Martinez A, et al (1998) Lipoxygenase inhibitors prevent lung carcinogenesis and inhibit non-small cell lung cancer growth. Exp Lung Res 24:617–628

    Article  PubMed  CAS  Google Scholar 

  • Omenn GS (1998) Chemoprevention of lung cancer: The rise and demise of beta-carotene. Annu Rev Public Health 19:73–99

    Article  PubMed  CAS  Google Scholar 

  • Omenn GS, Goodman GE, Thornquist MD, et al (1996) Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular health. N Eng J Med 334:1150–1155

    Article  CAS  Google Scholar 

  • Parkin DM (2001) Global cancer statistics in the year 2000. Lancet Oncol 2:533–543

    Article  PubMed  CAS  Google Scholar 

  • Pastorino U, Infante M, Maioli M, et al (l993) Adjuvant treatment of stage I lung cancer with high-dose vitamin A. J Clin Oncol 11:1216–1222

    Google Scholar 

  • Raben D, Helfrich BA, Chan D, et al (2002) ZD1839, a selective epidermal growth factor receptor tyrosine kinase inhibitor, alone and in combination with radiation and chemotherapy as a new therapeutic strategy in non-small cell lung cancer. Sem Oncol 29:37–46

    Article  CAS  Google Scholar 

  • Rioux N and Castonguay A (1998a) Prevention of NNK-induced lung tumorigenesis in A/J mice by acetylsalicylic acid and NS-398. Cancer Res 58:5354–5360

    PubMed  CAS  Google Scholar 

  • Rioux N and Castonguay A (1998b) Inhibitors of lipoxygenase: A new class of cancer chemopreventive agents. Carcinogenesis 19:1393–1400

    Article  PubMed  CAS  Google Scholar 

  • Saccomanno G, Archer VE, Auerbach O, et al (l974) Development of carcinoma of the lung as reflected in exfoliated cells. Cancer 33:256–270

    Article  Google Scholar 

  • Schreinemachers DM, Everson RB (1994) Aspirin use and lung, colon, and breast cancer incidence in a prospective study. Epidemiology 5:138–146

    Article  PubMed  CAS  Google Scholar 

  • Shureiqi I, Lippman SM (2001) Lipoxygense modulation to reverse carcinogenesis. Cancer Res 61:6307–6312

    PubMed  CAS  Google Scholar 

  • Steele VE, Holmes CA, Hawk ET, et al (1999) Lipoxygenase inhibitors as potential cancer chemopreventives. Cancer Epidemiol Biomarkers Prev 8:467–483

    PubMed  CAS  Google Scholar 

  • Steinbach G, Lynch PM, Phillips RKS, et al (2000) The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Eng J Med 342:1946–1952

    Article  CAS  Google Scholar 

  • Szabo E, Shaw GL (l997) Intermediate markers and molecular genetics of lung carcinogenesis Cancer Control 4:109–117

    Google Scholar 

  • Tong L, Spitz MR, Fueger JJ, et al (1996) Lung carcinoma in former smokers. Cancer 78:1004–1010

    Article  PubMed  CAS  Google Scholar 

  • Van Zandwijk N, Dalesio O, Pastorino U, et al (2000) EUROSCAN, a randomized trial of vitamin A and N-acetylcysteine in patients with head and neck cancer or lung cancer. J Natl Cancer Inst 92:977–986

    Article  PubMed  Google Scholar 

  • Watkins ON, Lenzo JC, Segal A, et al (1999) Expression and localization of cyclo-oxygenase isoforms in non-small cell lung cancer. Eur Respir J 14:412–418

    Article  PubMed  CAS  Google Scholar 

  • Wattenberg LW, Wiedmann TS, Estensen RD, et al (2000) Chemoprevention of pulmonary carcinogenesis by brief exposures to aerosolized budesonide or beclomethasone dipropionate and by the combination of aerosolized budesonide and dietary myo-inositol. Carcinogenesis 21:179–182

    Article  PubMed  CAS  Google Scholar 

  • Wolff H, Saukkonen K, Anttila S, et al (l998) Expression of cyclooxygenase-2 in human lung carcinoma. Cancer Res 58:4997–5001

    Google Scholar 

  • Xu X-C (2002) COX-2 inhibitors in cancer treatment and prevention, a recent development. Anticancer Drugs 13:127–137

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Szabo, E., Kalebic, T. (2003). Chemoprevention of Lung Cancer: New Directions. In: Senn, HJ., Morant, R. (eds) Tumor Prevention and Genetics. Recent Results in Cancer Research, vol 163. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-55647-0_16

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-55647-0_16

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-62892-4

  • Online ISBN: 978-3-642-55647-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics