Apoptosis: Its Role in the Development of Malignancies and its Potential as a Novel Therapeutic Target

Annals of Pharmacotherapy - Tập 31 Số 1 - Trang 76-82 - 1997
S C Dixon1, Benjamin J. Soriano, Richard M. Lush, Markus Borner, William D. Figg
1Clinical Pharmacokinetics Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Tóm tắt

OBJECTIVE:To review the current literature regarding the role of apoptosis in the development of malignant cells and how the induction of this pathway could be used in cancer therapy.DATA SOURCE:A MEDLINE search of basic science articles pertinent to the understanding of the normal physiologic process of apoptosis was conducted.STUDY SELECTION:Because of the rapidly growing literature regarding apoptosis, only articles describing key processes in the biology of the cell and the genetic control of apoptosis were included.DATA SYNTHESIS:Apoptosis is imperative for host survival since it discards unwanted, damaged, and atypical cells. The process is therefore implicated in the continuous regulation of development, differentiation, and homeostasis. Furthermore, apoptosis is a response to physiologic and pathologic stresses that disrupt the balanced rates of cell generation and elimination. In a disease such as cancer, there is a lack of equilibrium between the rates of cell division and cell death; agents that promote or suppress apoptosis can manipulate these rates, influencing the anomalous accumulation of neoplastic cells. Pharmacologic manipulation of apoptosis represents a novel approach in targeting malignant cells and has far-reaching implications for new directions in cancer therapy.CONCLUSIONS:Apoptosis is a highly organized physiologic mechanism of destroying injured and abnormal cells as well as maintaining homeostasis in multicellular organisms. Both the activation and inhibition of apoptosis are tightly controlled. Pharmacologic manipulation of this pathway is a novel therapeutic target in cancer therapy.

Từ khóa


Tài liệu tham khảo

10.1038/bjc.1972.33

Fesus L, 1991, Eur J Cell Bio, 56, 170

10.1016/S0065-2776(08)60487-3

Young AR, 1987, Photodermatology, 4, 127

10.1111/j.1365-2133.1982.tb00385.x

10.1111/j.1365-2141.1995.tb05308.x

10.1080/095530096146174

10.1269/jrr.36.203

Harney JV, 1995, Cancer Epidemiol Biomarkers Prev, 4, 617

10.1259/0007-1285-68-813-997

Vincent PC, 1995, Stem Cells (Dayt), 13, 153

Sakaguchi Y, 1995, Cancer Res, 55, 5459

10.1139/o94-064

Swanson PE, 1995, Am J Pathol, 146, 963

10.1016/0304-3835(94)03668-9

10.1016/0959-8049(94)00362-9

Schepotin IB, 1994, Anticancer Res, 14, 1027

10.1006/cimm.1995.1076

10.1016/0140-6736(93)91154-E

10.1007/BF00048059

10.1210/endo-122-2-552

Kyprianou N, 1991, Cancer Res, 51, 162

Redding TW, 1991, Cancer Res, 52, 2538

Laster SM, 1988, J Immunol, 141, 2629, 10.4049/jimmunol.141.8.2629

10.1016/0092-8674(92)90532-H

10.1038/377348a0

10.1074/jbc.270.40.23293

10.1182/blood.V83.7.1731.1731

10.1038/352345a0

10.1002/1097-0142(19940415)73:8<2013::AID-CNCR2820730802>3.0.CO;2-J

10.1073/pnas.87.17.6594

10.1016/0012-1606(91)90447-B

10.1016/0531-5565(92)90026-V

10.1016/0012-1606(92)90275-L

10.1523/JNEUROSCI.10-02-00403.1990

10.1007/BF00187906

Antalikova L, 1989, Folia Biol (Praha), 35, 339

10.1002/ar.1092330403

10.1159/000146099

10.1111/j.1600-065X.1991.tb00822.x

10.1016/B978-0-12-364932-4.50010-1

10.1007/BF00048057

10.1146/annurev.iy.10.040192.001411

10.1073/pnas.90.3.786

10.1002/med.2610150404

10.1002/path.1711190305

10.1159/000298983

10.1016/0002-9378(90)90923-U

10.1006/excr.1995.1131

10.1128/JVI.69.6.3955-3958.1995

10.1016/S0959-437X(95)90061-6

10.1038/376017a0

Petito CK, 1995, Am J Pathol, 146, 1121

Ucker DS, 1991, New Biol, 3, 103

10.1002/j.1460-2075.1993.tb06042.x

Wyllie AH, 1987, Int Rev Cytol, 17, 755

10.1007/BF00048064

10.1016/0167-5699(90)90048-E

Cohen JJ, 1984, J Immunol, 132, 38, 10.4049/jimmunol.132.1.38

Gaido ML, 1991, J Biol Chem, 266, 18580, 10.1016/S0021-9258(18)55102-4

10.1006/abbi.1993.1060

10.1016/0012-1606(77)90158-0

Korsmeyer SJ, 1992, Cancer Sur, 15, 105

10.1101/SQB.1994.059.01.043

10.1016/0092-8674(92)90123-T

10.1016/S0140-6736(95)91693-8

10.1101/SQB.1994.059.01.032

10.1016/0955-0674(95)80066-2

10.1016/0092-8674(93)90508-N

10.1016/0092-8674(93)90509-O

10.1038/369321a0

10.1006/excr.1995.1177

10.1038/376037a0

10.1126/science.7535475

10.1126/science.7878463

10.1073/pnas.92.20.9042

10.1016/0092-8674(95)90490-5

10.1083/jcb.123.1.7

10.1016/0092-8674(95)90541-3

10.1016/0092-8674(94)90518-5