Genotypic characteristics of resistant tumors to pre-operative ionizing radiation in rectal cancer

Abstract

Due to a wide range of clinical response in patients undergoing neo-adjuvant chemoradiation for rectal cancer it is essential to understand molecular factors that lead to the broad response observed in patients receiving the same form of treatment. Despite extensive research in this field, the exact mechanisms still remain elusive. Data raging from DNA-repair to specific molecules leading to cell survival as well as resistance to apoptosis have been investigated. Individually, or in combination, there is no single pathway that has become clinically applicable to date. In the following review, we describe the current status of various pathways that might lead to resistance to the therapeutic applications of ionizing radiation in rectal cancer.

Keywords: Ionizing radiation, DNA double-strand break, Non-homologous end-joining pathway, DNA-PKcs, Ku proteins, Complete pathological response, Radiation therapy, Apoptosis, Angiogenesis

Core tip: Treatment of locally advanced rectal cancer stage II and III includes neoadjuvant chemo-radiation followed by surgery if clinically feasible. A strategy of observing patients without an operation has been proposed by some surgeons, but this is still the center of much debate. Moreover, the therapeutic effect of ionizing radiation in treatment of rectal cancer varies significantly from one person to another. This has led investigators to identify the molecular targets and pathways in rectal tumors resistant to ionizing radiation in a bid to improve the therapeutic effect of radiation by advanced biomedical and genetic engineering.