Pilot study examining tumor expression of RAD51 and clinical outcomes in human head cancers

Abstract

Radiation therapy and chemotherapy are commonly used treatments for head and neck cancer. RAD51 is a highly conserved DNA repair protein that serves a central function in the homologous recombination pathway. High levels of RAD51 protein expression have been reported in number of human cancer cell lines, and studies suggest that RAD51 overexpression can increase cellular resistance to radiation and some chemotherapeutic drugs. In this study, RAD51 protein levels were quantified by immunohistochemistry in tumor samples from twelve head and neck cancer patients who received identical treatment with induction chemotherapy (paclitaxel and carboplatinum) followed by radiation therapy given concurrently with additional chemotherapy (paclitaxel, fluorouracil, hydroxyurea). Patients with high RAD51 protein levels in their pre-treatment tumor biopsies demonstrated poorer cancer-specific survival rates than patients with lower RAD51 levels (33.3% vs. 88.9% at 2 years; p=0.025). In addition, within a subgroup of patients with normal tumor cell p53 expression, there was a non-significant trend toward better induction chemotherapy response rates observed in the tumors with lower RAD51 protein levels. These results suggest that tumor cell RAD51 expression levels may influence the outcome of patients with head and neck cancer treated with chemotherapy and radiotherapy.

Role of the RAD51 G172T polymorphism in the clinical outcome of cervical cancer patients under concomitant chemoradiotherapy

“…RAD51 has been found to be increased in expression in a wide range of human tumors, most likely contributing to chemotherapeutic resistance of these tumors (Klein, 2008). According to previous studies in other tumor models, the study of RAD51 gene seems to be important for the prediction of treatment response with chemotherapeutic drugs (Connell et al, 2006). It remains unclear whether the link of RAD51 expression to sensitivity to platinum agents may affects the prognosis (Takenaka et al, 2007).…”

Role of repair protein Rad51 in regulating the response to gefitinib in human non-small cell lung cancer cells

“…Overexpression of Rad51 protein in mammalian cells confers resistance to ionizing radiation, and Rad51 participates in the repair of doublestrand breaks by homologous recombination involving sister chromatids formed after the S phase (23). High levels of Rad51 are correlated with resistance to chemotherapeutic agents and poor prognostic outcome (29,47). In NSCLC, high expression of Rad51 is associated with an unfavorable prognosis and resistance to platinum agents (48,49).…”

Applications of Fluorescence for Detecting Rare Sequence Rearrangements In Vivo

“…[24][25][26][27][28][29] Interestingly, elevated levels of HR proteins within tumor cells are associated with an increased resistance to many cancer chemotherapeutics [30][31][32][33][34][35] and a poor prognosis for cancer survival. 36 In contrast, cancer cells deficient in HR (e.g., breast tumors with BRCA2 mutations 37,38 ) are rendered sensitive to chemotherapeutic agents that induce replication fork breakdown. [39][40][41][42] Therefore, knowledge about HR capacity is relevant both to one's risk of developing cancer 13,14,19 and to the response of a tumor to chemotherapy.…”