Radioresistance in carcinoma of the breast.
Radiotherapy plays an important role in the management of breast cancer. Whilst its role in achieving local control following surgery in patients with early stage cancer is well established, there is still unclear evidence to explain the factors governing radioresistance in patients who develop recurrences both in the breast and axilla. Radiotherapy induces damage to the DNA. Various cell cycle damage check points and DNA damage repair pathways have been demonstrated. Ataxia telangiectasia mutant (ATM) kinase, which is a member of phosphatidylinositol-3 kinase (PI-3K) family appears to play a central role in DNA damage check point pathways. Over-expression of Insulin like growth factor-I receptor (IGF-IR), Human Epidermal Growth factor receptors (HERS), Vascular Endothelial growth factor (VEGF) on the cell surface and increased concentration of Epidermal Growth factor in the extracellular fluid have been associated with radioresistance. Specific genes such as p53, BRCA, Bcl-2 and chromosomal characteristics like telomere lengths have also been identified as playing significant roles in radiation responsiveness of a cell. This article reviews the current data on general principles of radiotherapy, the cellular mechanisms that operate in response to radiation damage and various molecular markers, intranuclear and extranuclear which have been demonstrated to influence radiation sensitivity in breast cancer cells.
Jameel
J K A
JK
Academic Surgical Unit, Castle Hill Hospital, Cottingham, East Yorkshire, HU16 5JQ, UK.
Rao
V S R
VS
Cawkwell
L
L
Drew
P J
PJ
D064007:Ataxia Telangiectasia Mutated Proteins; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D002352:Carrier Proteins / Q000235:genetics; D018797:Cell Cycle Proteins; D004249:DNA Damage; D004268:DNA-Binding Proteins; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases
D024682:BRCA2 Protein; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C111164:BRAP protein, human; D044767:Ubiquitin-Protein Ligases; D066246:ErbB Receptors; D017526:Receptor, IGF Type 1; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases