DNA damage response and growth factor signaling pathways in gliomagenesis and therapeutic resistance Journal Article
| Authors: | Squatrito, M.; Holland, E. C. |
| Article Title: | DNA damage response and growth factor signaling pathways in gliomagenesis and therapeutic resistance |
| Abstract: | The dismal prognosis of glioblastoma multiforme (GBM) is mainly due to the poor response of GBM patients to any therapeutic modalities, which include ionizing radiation and DNA-alkylating agents. In the last few years, the important role of the DNA damage response (DDR) pathway in tumor formation and modulation of therapeutic response has been appreciated. Interestingly, several of the genetic alterations commonly found in GBMs (such as epidermal growth factor receptor amplification and PTEN inactivation) have also recently been shown to regulate the activity of the DNA repair machinery and, consequently, the response to DNA-damaging agents used routinely in the clinic. In this review, we focus on some of these findings that suggest that at least some of the pathways driving GBM formation could be directly responsible for the therapy resistance of this tumor type. Possible therapeutic approaches exist that may either overcome or take advantage of these GBM genetic alterations to improve the response of these tumors to DNA-damaging therapy. ©2011 AACR. |
| Keywords: | signal transduction; platelet derived growth factor; cancer survival; protein phosphorylation; treatment response; intercellular signaling peptides and proteins; unclassified drug; overall survival; review; cisplatin; drug potentiation; nonhuman; cancer radiotherapy; temozolomide; antineoplastic agent; cell proliferation; animals; dna damage; cell survival; dna repair; apoptosis; etoposide; epidermal growth factor receptor; drug resistance, neoplasm; protein tyrosine kinase; cetuximab; phosphatidylinositol 3 kinase; protein p53; central nervous system neoplasms; carcinogenesis; gene rearrangement; drug mechanism; mismatch repair; glioblastoma; enzyme inactivation; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; gefitinib; cell migration; atm protein; ionizing radiation; cell cycle arrest; neurofibromin; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase inhibitor; radiosensitivity; double stranded dna break; excision repair; checkpoint kinase 2; cell cycle g2 phase; cell cycle m phase; gene silencing; heterozygosity loss; methylated dna protein cysteine methyltransferase; receptor blocking; checkpoint kinase 1; growth factor; atr protein; histone h2ax; radiation tolerance; 4 (3 chloroanilino) 6,7 dimethoxyquinazoline; 8 fluoro 3,4 dihydro 2 [4 (methylaminomethyl)phenyl]pyrrolo[3,4,5 e,f][2]benzazepin 6(5h) one; dna dependent protein kinase; veliparib; cep 6800; gp 15427 |
| Journal Title: | Cancer Research |
| Volume: | 71 |
| Issue: | 18 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2011-09-15 |
| Start Page: | 5945 |
| End Page: | 5949 |
| Language: | English |
| DOI: | 10.1158/0008-5472.can-11-1245 |
| PROVIDER: | scopus |
| PUBMED: | 21917735 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 3 October 2011" - "CODEN: CNREA" - "Source: Scopus" |
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