Targeting nonhomologous end-joining through epidermal growth factor receptor inhibition: Rationale and strategies for radiosensitization

Bipasha Mukherjee, Hak Choy, Chaitanya Nirodi, Sandeep Burma

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

DNA double-strand breaks (DSBs) are the most lethal type of DNA damage induced by ionizing radiation or chemotherapeutic drugs used to eradicate cancer cells. The ability of cancer cells to effectively repair DSBs significantly influences the outcome of therapeutic regimens. Therefore, a new and important area of clinical cancer research is the development of DNA repair inhibitors that can be used as radio- or chemosensitizers. Nonhomologous end joining (NHEJ) is the predominant pathway for the repair of radiation-induced DSBs. A series of recent reports indicates that the epidermal growth factor receptor (EGFR) or its downstream components may modulate NHEJ through direct interaction with the DNA repair enzyme, DNA-dependent protein kinase. Because EGFR is overexpressed or activated in many cancers, these findings provide a compelling rationale for combining radiotherapy with therapies that block EGFR or its downstream signaling components. In this review, we delineate how these novel connections between a cell-surface receptor (EGFR) and a predominantly nuclear event (NHEJ) provide vulnerable nodes that can be selectively targeted to improve cancer therapy.

Original languageEnglish (US)
Pages (from-to)250-257
Number of pages8
JournalSeminars in Radiation Oncology
Volume20
Issue number4
DOIs
StatePublished - Oct 2010

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Epidermal Growth Factor Receptor
Neoplasms
DNA-Activated Protein Kinase
DNA Repair Enzymes
Double-Stranded DNA Breaks
Cell Surface Receptors
Ionizing Radiation
Radio
DNA Repair
DNA Damage
Radiotherapy
Therapeutics
Radiation
Research
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Targeting nonhomologous end-joining through epidermal growth factor receptor inhibition : Rationale and strategies for radiosensitization. / Mukherjee, Bipasha; Choy, Hak; Nirodi, Chaitanya; Burma, Sandeep.

In: Seminars in Radiation Oncology, Vol. 20, No. 4, 10.2010, p. 250-257.

Research output: Contribution to journalArticle

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