Article information
RESUMO
No presente artigo de revisão o autor relata os conhecimentos actuais sobre a biologia celular e molecular do cancro do pulmão, relacionandoos, sempre que possível, com as respectivas implicações diagnósticas, prognósticas e terapêuticas.
REV PORT PNEUMOL 2002; VIII (6): 655-679
Palavras-chave:
Cancro do pulmão
biologia celular
biologia molecular
transformação maligna
progressão tumoral
metastização
ABSTRACT
In this revision article the author stats about the celular and molecular biology of lung cancer and his relation with the diagnosis, evolution, prognosis and therapeutics of the disease.
REV PORT PNEUMOL 2002; VIII (6): 655-679
Key-words:
Lung cancer
molecular biology
celular biology
malignant transformation
tumoral progression
metastatic spread
Full text is only aviable in PDF
BIBLIOGRAFIA
[1.]
H. Aikawa, H. Takahashi, S. Fujimura, et al.
Immunohistochemical study on tumor angiogenic factors in non-small cell lung cancer.
Anticancer Res, 19 (1999), pp. 4305-4309
[2.]
F. Albanell, V. Leonardo, M. Rusch, et al.
High telomerase activity in primary lung cancers: association with increased cell proliferation rates and advanced pathologic stage.
J Natl Cancer Inst, 89 (1997), pp. 1609-1615
[3.]
J.C. Bailar, H.L. Gornik.
Cancer undefeated.
New Engl J Med, 336 (1997), pp. 1569-1574
[4.]
J. Bergh, R. Larsson, P. Nygren.
Resistance to chemotherapeutic drugs in human lung cancer: is circumvention possible?.
Lung Cancer, 9 (1993), pp. 307-316
[5.]
Second International Workshop on Small Cell Lung Cancer Antigens.
P.C.L.BeverlyL.G.BobrowR.S.Souhami. Br J Cancer, 63 (1991),
[6.]
J.M. Boers, G.P.M.T. Velde, F.J.B. Thunnissen.
P53 in squamous metaplasia: A marker for risk of respiratory tract carcinoma.
Am J Crit Care Med, 153 (1996), pp. 411-416
[7.]
P. Bonomi.
Novel approaches for the treatment of non-small cell lung cancer.
Semin Oncol, 28 (2001), pp. 45-49
[8.]
E. Brambilla, S. Gazzeri.
P53 Pathway and lung cancer.
Lung Tumors, pp. 173-190
[9.]
P.A. Bunn, K. Kelly.
Antigens in lung cancer: clinical radioimmunolocalization in lung cancer.
Lung Cancer, 9 (1993), pp. 171-178
[10.]
P.T. Cagle, A.K. El-Naggar Ak, H.J. Xu, et al.
Differential retinoblastoma protein expression in neuroendocrine tumors of lung. Potential diagnostic implications.
Am J Pathol, 150 (1997), pp. 303-400
[11.]
N.E. Caporaso, M.A. Tucker, R.N. Hoover, et al.
Lung cancer and the debrisoquine metabolic phenotype.
J Natl Cancer Inst, 82 (1990), pp. 1264-1272
[14.]
D.N. Carney.
Lung cancer biology.
Semin Radiot Oncol, 5 (1995), pp. 4-10
[15.]
D.N. Carney, J.B. Mitchell, T.J. Kinsella.
In vitro radiation and chemotherapy sensitivity of established cell lines of human small cell lung cancer and its large cell morfological variants.
Cancer Res, 43 (1983), pp. 2806-2811
[16.]
D.C. Chan, A. Soriano, M.A. Kane, et al.
Biology of Lung Cancer.
Textbook of Lung Cancer, pp. 27-73
[17.]
J.T. Cooke, R.G. Crystal.
Genetic basis of lung cancer.
The Lung: Scientific Foundations, Second Edition, pp. 2589-2597
[18.]
C.A. Cooper, F.A. Carey, V.J. Bubb, et al.
The pattern of K-ras mutation in pulmonary adenocarcinoma defines a new pathway of tumour development in the human lung.
J Pathol, 181 (1997), pp. 401-404
[19.]
D.G. Davila, D.E. Williams.
The etiology of lung cancer.
Mayo Clin Proc, 68 (1993), pp. 505-513
[20.]
T.R. Devereux, J.A. Taylor, J.C. Barret.
Molecular mechanisms of lung cancer.
Chest, 109 (1996), pp. 14S-19S
[21.]
X. Dong, L. Mao.
Molecular Biology of Human Lung Cancer: A Detailed Analysis.
Current Clinical Oncology: Cancer of the Lung, pp. 103-127
[22.]
H. Dosaka-Akita, H.U. S-H, M. Fujino, et al.
Altered retinoblastoma protein expression in nonsmall cell lung cancer. Its synergistic effects with altered ras and p53 protein status on prognosis.
Cancer, 79 (1997), pp. 1329-1337
[23.]
L.A. Doyle.
Mechanisms of drug resistance in human lung cancer cells.
Semin Oncol, 20 (1993), pp. 326-337
[24.]
S.M. Dubinett, P.W. Miller, S. Sharma, et al.
Gene therapy for lung cancer.
Hematol Oncol Clin North Am, 12 (1998), pp. 569-594
[25.]
R. Duggira, L. Almasy, J. Blangero.
Smoking behavior is under the influence of a major quantitative trait locus on human chromosome 5q.
Genet Epidemiol, 17 (1999), pp. S139-S144
[26.]
T. Eisen.
The biology of lung cancer.
Eur Respir Mon, 17 (2001), pp. 61-70
[27.]
M. Fleischhacker, T. Beinert, K. Possinger.
Molecular genetic characteristics of lung cancer – useful as “real” tumor markers?.
Lung Cancer, 25 (1999), pp. 7-24
[28.]
F. Fong, P. Zimmerman, P. Smith.
Lung pathology: the molecular genetics of non-small cell lung cancer.
Pathology, 27 (1995), pp. 295-301
[29.]
T. Fujiwara, E.A. Grimm, T. Mukhopadhyay, et al.
Induction of chemosensitivity in human lung cancer in vivo by adenovirus-mediated transfer of the wildtype o53 gene.
Cancer Res, 54 (1994), pp. 2287-2291
[30.]
O. Geneste, A.M. Camus, M. Castegnaro, et al.
Comparison of pulmonary DNA adduct levels, measured by 32p-postlabelling and aryl hydrocarbon hydroxylase activity in lung parenchyma of smokers and ex-smokers.
Carcinogenesis, 12 (1991), pp. 1301-1305
[31.]
J. Hansson.
Mechanisms of tumor cell resistance to cancer chemotherapeutic drugs.
Eur J Surg, 561 (1991), pp. 35-44
[32.]
M. Harada, H. Dosoka-Akita, H. Miyamoto, et al.
Prognostic significance of the expression of ras oncogene product in non-small cell lung cancer.
Cancer, 69 (1992), pp. 72-77
[33.]
J. Harbour, S. Lai, J. Whang-Peng, et al.
Abnormalities in structure and expression of retinoblastoma gene in SCLC.
Science, 241 (1988), pp. 353-357
[34.]
D. Harpole, W. Richards, J. Herndon, et al.
Angiogenesis and molecular biologic substaging in patients with stage I non-sall cell lung cancer.
Ann Thorac Surg, 61 (1996), pp. 1470-1476
[36.]
S.S. Hecht, D. Hoffmann.
Tobacco-specific nitrosamines, an important group of carcinogens in tobacco and tobacco smoke.
Carcinogenesis, 9 (1988), pp. 875-884
[37.]
K. Hibi, T. Takahashi, K. Yamakawa, et al.
Three distinct regions involved in 3p deletion in human lung cancer.
Oncogene, 7 (1992), pp. 445-449
[38.]
E.A. Hirschowitz, R.G. Crystal.
Biology of lung cancer.
The Lung: Scientific Foundation, Second Edition, pp. 2579-2588
[39.]
K. Hiyama, S. Ishioka, Y. Shirotani, et al.
Alterations in telomeric repeat lenght in lung cancer are associated with loss of heterozygosity in p53 and rb.
Oncogene, 10 (1995), pp. 937-944
[40.]
D. Hoffmann, S.S. Hecht.
Advances in tobacco carcinogenesis.
Handbook of Experimental Pharmacology, pp. 63-107
[41.]
D.R. Jacobson.
Ras mutations in lung cancer.
Lung Tumors, pp. 139-156
[42.]
B.E. Johnson, M.J. Kelley.
Biology and molecular genetics of lung cancer.
Semin Respir Crit Care Med, 17 (1996), pp. 299-308
[43.]
P. Johnson, S. Joel, S. Love, et al.
Tumor markers for prediction of survival and monitoring of remission in small cell lung cancer.
Br J Cancer, 67 (1993), pp. 760-766
[44.]
M. Kawasaki, Y. Nakanishi, Kuwano, et al.
Immunohistochemically detected p53 and P-glycoprotein predict the response to chemotherapy in lung cancer.
Eur J Cancer, 34 (1998), pp. 1352-1357
[45.]
M.J. Kelley, B.E. Johnson.
Molecular genetics of lung cancer.
Lung Cancer, pp. 246-266
[46.]
J. Kern, D. Schwartz, J. Nordberg, et al.
p185neu expression in human lung adenocarcinomas predicts shortened survival.
Cancer Res, 50 (1990), pp. 5184-5191
[47.]
S.A. Khuder, A.B. Mutgi.
Effect of smoking cessation on major histologic typs of lung cancer.
Chest, 120 (2001), pp. 1577-1583
[48.]
R. Kibbelaar, C. Moolenaar, R. Michalides, et al.
Expression of the embryional neural cell addesion molecule N-CAM in lung carcinoma. Diagnostic usefulness of monoclonal antibody 735 for the distinction between small cell lung cancer and non-small cell lung cancer.
J Pathol, 159 (1989), pp. 23-28
[49.]
D. Kirsch, M.B. Kastan.
Tumor-suppressor p53. Implications for tumor development and prognosis.
J Clin Oncol, 16 (1998), pp. 3158-3168
[50.]
H. Kohno, K. Hiroshima, T. Toyozaki, et al.
p53 mutation and allelic loss of chromosome 3p,9p of preneoplastic lesions in patients with nonsmall cell lung carcinoma.
Cancer, 85 (1999), pp. 341-347
[51.]
S. Korsmeyer.
Regulators of cell death.
Trends Genet, 11 (1995), pp. 101-105
[52.]
J.Á. Lederman, D. Ornadel.
The biology of lung cancer.
Eur Respir Mon, 1 (1995), pp. 72-90
[53.]
J. Lee, J. Ro, A. Sahin, et al.
Expression of blood group antigen A: a favourable prognostic factor in non-small cell lung cancer.
N Engl J Med, 324 (1991), pp. 1084-1090
[54.]
J. Lee, A. Yoon, S. Kalapurakal, et al.
Expression of p53 oncoprotein in non-small-cell lung cancer: a favorable prognostic factor.
J Clin Oncol, 13 (1995), pp. 1893-1903
[55.]
J.C. Lee, H.S. Jong, C.G. Yoo, et al.
Telomerase activity in lung cancer cell lines and tissues.
Lung Cancer, 21 (1998), pp. 99-103
[56.]
S. Lowe, S. Bodis, A. McClatchey, et al.
p53 status and the efficacy of cancer therapy in vivo.
Science, 266 (1994), pp. 807-810
[57.]
R. Lubin, G. Zalcman, L. Bouchet, et al.
Serum p53 antibodies as early markers of lung cancer patients.
Nature Med, 1 (1995), pp. 701-702
[58.]
P. Macchiarini, G. Fontanini, J. Hardin, et al.
Most peripheral, node-negative, non-small-cell lung cancers have low proliferative rates and no intratumoral and peritumoral blood and lymphatic vessel invasion.
J Thorac Cardiovasc Surg, 104 (1992), pp. 892-899
[59.]
R. Maneckjee, J.D. Minna.
Opioid and nicotine receptors affect growth regulation of human lung cancer cell lines.
Proc Natl Acad Sci, 87 (1990), pp. 3294-3298
[60.]
R. Maneckjee, J.D. Minna.
Opioids induce while nicotine suppresses apoptosis in human lung cancer cells.
Cell Growth Differ, 5 (1994), pp. 1033-1040
[61.]
L. Mao, J.S. Lee, J.M. Kurie, et al.
Clonal genetic alterations in the lungs of current and former smokers.
J Natl Cancer Inst, 89 (1997), pp. 857-862
[62.]
J. Mattern, R. Koomagi, M. Volm.
Association of vascular endothelial growth factor expression with intratumoral microvessel density and tumour cell proliferation in human epidermoid lung carcinoma.
Br J Cancer, 73 (1996), pp. 931-934
[63.]
T.L. Mclemore, S. Adelberg, M. Czerwinski, et al.
Altered regulation of the cytochrome p4501a1 gene: Novel inducer-independent gene expression in pulmonary carcinoma cell lines.
J Natl Cancer, 81 (1989), pp. 1787-1794
[64.]
S.A. Mehdi, A.A. Tatum, N.B. Newman, et al.
Prognostic significance of LewisY antigen in resected stage I and II non-small cell lung cancer.
Chest, 114 (1998), pp. 1309-1315
[65.]
A. Merlo, E. Gabrielson, F. Askin, et al.
Frequent loss of chromosome 9 in human primary non-small cell lung cancer.
Cancer Res, 54 (1994), pp. 640-642
[66.]
M. Mikaye, T. Taki, S. Hitomi, et al.
Correlation of expression of H/ Le y /Le b antigens with survival in patients with carcinoma of the lung.
N Engl J Med, 327 (1992), pp. 14-18
[67.]
K.D. Miller, C.J. Sweeney, G.W. Sledje Jr..
Redefining the target: Chemotherapeutics as antiangiogenics.
J Clin Oncol, 19 (2001), pp. 1195-1206
[68.]
J.D. Minna.
The molecular biology of lung cancer pathogenesis.
Chest, 103 (1993), pp. 449S-456S
[69.]
T. Mitsudomi, T. Oyama, T. Kusano, et al.
Mutations of the p53 gene as a predictor of poor prognosis in patients with non-small-cell lung cancer.
J Natl Cancer Inst, 85 (1993), pp. 2018
[70.]
V. Nazar-Stewart, A.G. Motulsky, D.L. Eaton, et al.
The glutathione s-transferase mu polymorphism as a marker for susceptibility to lung carcinoma.
Cancer Res, 53 (1993), pp. 2313-2318
[71.]
H. Ohata, M. Emi, Y. Fujiwara, et al.
Deletion mapping of the short arm of chromosome 8 in non-small cell lung carcinoma.
Genes Chrom Cancer, 7 (1993), pp. 85-88
[72.]
Y. Ohsaki, E. Toyoshima, S. Fujiuchi, et al.
bcl-2 and p53 protein expression in non-small cell lung cancers correlation with survival time.
Clin Cancer Res, 2 (1996), pp. 915-920
[73.]
Y. Ohta, S. Watanabe, M. Murukami, et al.
Vascular endothelial growth factor and lymph node metastasis in primary lung cancer.
Br J Cancer, 76 (1997), pp. 1041-1045
[74.]
G. Otterson, A. Lin, F. Kaye.
Genetic etiology of lung cancer.
Oncology, 6 (1992), pp. 97-112
[75.]
G.A. Otterson, R.A. Kratzke, A. Coxon, et al.
Absence of p16INK4 protein is restricted to the subset of lung cancer lines that retains wildtype RB.
Oncogene, 9 (1994), pp. 3375-3378
[76.]
F. Pezzela, H. Turley, I. Kuzu, et al.
bcl-2 protein in non-small-cell lung carcinoma.
N Engl J Med, 329 (1993), pp. 690-694
[77.]
R.M. Przygodzki, S.D. Finkelelstein, J.C. Langer, et al.
Analysis of p53, K-ras, and C-raf-1 in pulmonary neuroendocrine tumors.
Am J Pathol, 148 (1996), pp. 1531-1541
[78.]
P.H. Rabbitts.
Genetic changes in the development of lung cancer.
Br Med Bull, 50 (1994), pp. 688-697
[79.]
M.J. Renan.
How many mutations are required for tumorigenesis? Implications from human cancer data.
Mol Carcinog, 7 (1993), pp. 139-146
[80.]
G.E. Richardson, B.E. Johnson.
The biology of lung cancer.
Semin Oncol, 20 (1993), pp. 105-127
[81.]
H.L. Rodrigues.
Mecanismos de fármaco resistência no cancro do pulmão.
Pneumologia Oncológica, pp. 201-226
[82.]
W.N. Rom, J.G. Hay, T.C. Lee, et al.
Molecular and genetic aspects of lung cancer.
Am J Respir Crit Care Med, 161 (2000), pp. 1355-1367
[83.]
J.A. Roth, S.F. Grammer, S.G. Swisher, et al.
Gene therapy approaches for the management of non-small cell lung cancer.
Semin Oncol, 28 (2001), pp. 50-56
[84.]
J.A. Roth, D. Nguyen, D.D. Lawrence, et al.
Retrovirus-mediated wild-type p53 gene transfer to tumors of patients with lung cancer.
Nature Med, 2 (1996), pp. 985-991
[85.]
R. Salgia, A. Skarin.
Lung cancer: from molecular biology to novel therapeutics.
Hosp Phys, 32 (1996), pp. 12-32
[86.]
R. Salgia, A. Skarin.
Molecular abnormalities in lung cancer.
J Clin Oncol, 16 (1998), pp. 1207-1217
[87.]
R. Salgia, A.T. Skarin.
Molecular and cellular biological abnormalities in lung cancer and the potential for novel therapeutics.
Multimodality treatment of lung cancer, pp. 3-25
[88.]
R. Salgia, A. Skarin, S. O’Day, et al.
CA 125: a useful tumor marker and an indicator of response to therapy in lung cancer.
Proc ASCO, 13 (1994), pp. 347a
[90.]
M. Seckl, T. Higgins, F. Widmer, et al.
[D-Arg1, D-Trp5,7,9, Leu11] substance P:a novel potent inhibitor of signal transduction and growth in vitro and in vivo in small cell lung cancer cells.
Cancer Res, 57 (1997), pp. 51-54
[91.]
Y. Sekido, K.M. Fong, J.D. Minna.
Progress in understanding the molecular pathogenesis of human lung cancer.
Biochim Biophys Acta, 1378 (1998), pp. F21-F59
[92.]
G. Shapiro, B. Rollins.
p16INK4A as a human tumor suppressor.
Biochim Biophys Acta, 1242 (1996), pp. 165-169
[93.]
H. Shibanuma, T. Hirano, K. Tsuji, et al.
Influence of E-cadherin dysfunction upon local invasion and metastasis in non-small cell lung cancer.
Lung Cancer, 8 (1999), pp. 85-95
[94.]
M. Shiseki, T. Kohno, R. Nishikawa, et al.
Frequent allelic loss on chromosomes 2q, 18q, and 22q in advanced nonsmall cell lung carcinoma.
Cancer Res, 54 (1994), pp. 5643-5648
[95.]
D. Sidransky, M. Hollstein.
Clinical implications of the p53 gene.
Annu Rev Med, 47 (1996), pp. 285-301
[96.]
R. Slebos, R. Kibbelaar, O. Dalesio, et al.
K-ras oncogene activation as a prognostic marker in adenocarcinoma of the lung.
N Engl J Med, 323 (1990), pp. 561-565
[97.]
R. Sotto-Mayor.
Terapêutica génica do cancro do pulmão.
Pneumologia Oncológica, pp. 227-236
[98.]
R. Sotto-Mayor.
Tumores neuroendócrinos do pulmão.
Oncologia Pneumológica/Temas de Actualização, pp. 301-320
[99.]
R. Sotto-Mayor.
Poluição e Cancro do pulmão.
Ambiente Urbano e Saúde (IV) – A Cidade, o Clima e os Cidadãos, pp. 111-131
[100.]
R. Sotto-Mayor.
Progressos terapêuticos no cancro do pulmão. Perspectiva actual e futura.
Monografia do 34º Curso de Pneumologia para Pós-Graduados, FML/HSM, (2001), pp. 23-46
[101.]
T. Soussi.
The p53 tumor supressor gene: From molecular biology to clinical investigation.
Lung Tumors, pp. 453-471
[102.]
G. Sozzi.
Deletions of the short arm of chromosome 3 and the FHIT gene in lung cancer.
Lung Tumors, pp. 157-171
[103.]
G. Sozzi, M. Miozzo, U. Pastorino, et al.
Genetic evidence for an independent origin of multiple preneoplastic and neoplastic lung lesions.
Cancer Res, 55 (1995), pp. 135-140
[104.]
G. Sozzi, M. Veronese, M. Negrini, et al.
The FHIT gene at 3p14.2 is abnormal in lung cancer.
Cell, 85 (1996), pp. 17-26
[105.]
R.A. Stahel.
Monoclonal antibodies to membrane antigens of lung cancer.
Lung Cancer, pp. 191-212
[106.]
R.A. Stahel, et al.
Third International Workshop on Lung –Tumour and Differentiation Antigens: Overview of the results and the central data analysis.
Int J Cancer, 8 (1994), pp. 6-26
[107.]
M. Stancu, T. King, A. Maizel.
Molecular Biology of Lung Cancer: A Primer.
Current Clinical Oncology: Cancer of the Lung, pp. 81-102
[108.]
K. Sugio, Y. Kishimoto, A.K. Virmani, et al.
K-ras mutations are a relatively late event in the pathogenesis of lung carcinoma.
Cancer Res, 54 (1994), pp. 5811-5815
[109.]
S.G. Swisher, J.Á. Roth, J. Nemunaitis, et al.
Ade-noviral-mediated p53 gene transfer in advanced non-small cell lung cancer.
J Natl Cancer Inst, 91 (1999), pp. 763-771
[110.]
L. Tong, M.R. Spitz, J.J. Fueger, et al.
Lung carcinoma in former smokers.
Cancer, 78 (1998), pp. 1004-1010
[111.]
G.E. Trivers, V.M.G. De Benedetti, H.L. Cawley, et al.
Anti-p53 antibodies in sera from patients with chronic obstructive pulmonary disease can predate a diagnosis of cancer.
Clin Cancer Res, 2 (1996), pp. 1767-1775
[112.]
P. Vineis, N. Caporaso.
Tobacco and cancer: Epidemiology and the laboratory.
Environ Health Perspect, 103 (1995), pp. 156-160
[113.]
D. Weil, M. Mack, J. Roth, et al.
Adenoviral-mediated p53 gene transfer to non-small cell lung cancer through endobronchial injection.
Chest, 118 (2000), pp. 966-970
[114.]
S.J. Weintraub.
Inactivation of tumor suppressor proteins in lung cancer.
Am J Respir Cell Mol Biol, 15 (1996), pp. 150-155
[115.]
W.H. Westra, R.J. Slebos, G.J. Offerhaus, et al.
K-ras oncogene activation in lung adenocarcinomas from former smokers. Evidence that K-ras mutations are an early and irreversible event in the development of adenocarcinoma of the lung.
Cancer, 72 (1993), pp. 432-438
[116.]
J. Whang-Peng, C.S. Kao-Shan, E.C. Lee, et al.
Specific chromosome defect associated with human smallcell lung cancer: delection 3p (14-23).
Science, 215 (1982), pp. 181-182
[117.]
I.I. Wistuba, S. Lam, C. Behrens, et al.
Molecular damage in the bronchial epithelium of current and former smokers.
J Natl Cancer Inst, 89 (1997), pp. 1366-1373
[118.]
K. Yashima, L. Litzky, T. Kaiser, et al.
Telomerase expression in respiratory epithelium during the multistage pathogenesis of lung carcinomas.
Cancer Res, 57 (1997), pp. 2373-2377
[119.]
J. Yokota, T. Akiyama, Y. Fung, et al.
Altered expression of the retinoblastoma (RB) gene in small cell lung cancer.
Oncogene, 3 (1988), pp. 471-475
[120.]
G. Zalcman, B. Schlchtholz, J. Tredaniel, et al.
Monitoring of p53 autoantibodies in lung cancer during therapy:relationship to response to treatment.
Clin Canc Res, 4 (1998), pp. 1359-1366
[121.]
W. Zhang, R. Alemany, J. Wang, et al.
Safety evaluation of adCMV-p53 in vitro and in vivo.
Hum Gene, 6 (1995), pp. 155-164
Copyright © 2002. Sociedade Portuguesa de Pneumologia/SPP
Open access
This work is licensed under a Creative Commons Attribution 4.0 International License.
Publish in
Pulmonology
Pulmonology
- Home
- All contents
- Publish your article
- About the journal
- Metrics
- Open access
Article options