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Ras has been shown to increase radiation resistance. Thus, upstream and downstream pathways from Ras could be targets for manipulation of radiosensitivity. Epidermal growth factor receptor (EGFR) expression and Akt phosphorylation are also associated with the response to radiation. A retrospective study evaluating EGFR and Akt in patients treated with multimodality therapy found a significant association between P-Akt and treatment failure. Moreover, these data are strengthened by in vitro studies showing that inhibition of EGFR, Ras, PI3K, and Akt radiosensitized cancer cell lines. We have previously shown that PI3K is a mediator of Ras-induced radiation resistance. We now suggest that EGFR, which is upstream of PI3K, may also mediate resistance through a common pathway. In addition to EGFR and Ras, PTEN can also regulate the PI3K pathway. Identifying a common signal for EGFR, Ras, or PTEN that results in radiation resistance may uncover targets for developing molecular-based radiosensitization protocols for tumors resistant to radiation and thus improve local control.

Type

Journal article

Journal

Semin Oncol

Publication Date

06/2003

Volume

30

Pages

56 - 67

Keywords

Alkyl and Aryl Transferases, Clinical Trials as Topic, Colorectal Neoplasms, Dimethylallyltranstransferase, Enzyme Inhibitors, ErbB Receptors, Farnesyltranstransferase, Humans, PTEN Phosphohydrolase, Phosphoric Monoester Hydrolases, Phosphorylation, Protein-Serine-Threonine Kinases, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-akt, Radiation Tolerance, Radiation-Sensitizing Agents, Signal Transduction, Treatment Failure, Tumor Suppressor Proteins, ras Proteins