Biomarkers for response to neoadjuvant chemoradiation for rectal cancer.
Locally advanced rectal cancer (LARC) is currently treated with neoadjuvant chemoradiation. Although approximately 45% of patients respond to neoadjuvant therapy with T-level downstaging, there is no effective method of predicting which patients will respond. Molecular biomarkers have been investigated for their ability to predict outcome in LARC treated with neoadjuvant chemotherapy and radiation. A literature search using PubMed resulted in the initial assessment of 1,204 articles. Articles addressing the ability of a biomarker to predict outcome for LARC treated with neoadjuvant chemotherapy and radiation were included. Six biomarkers met the criteria for review: p53, epidermal growth factor receptor (EGFR), thymidylate synthase, Ki-67, p21, and bcl-2/bax. On the basis of composite data, p53 is unlikely to have utility as a predictor of response. Epidermal growth factor receptor has shown promise as a predictor when quantitatively evaluated in pretreatment biopsies or when EGFR polymorphisms are evaluated in germline DNA. Thymidylate synthase, when evaluated for polymorphisms in germline DNA, is promising as a predictive biomarker. Ki-67 and bcl-2 are not useful in predicting outcome. p21 needs to be further evaluated to determine its usefulness in predicting outcome. Bax requires more investigation to determine its usefulness. Epidermal growth factor receptor, thymidylate synthase, and p21 should be evaluated in larger prospective clinical trials for their ability to guide preoperative therapy choices in LARC.
Kuremsky
Jeffrey G
JG
Institute for Pharmacogenomics and Individualized Therapy, University of North Carolina, Chapel Hill, NC 27599-7360, USA.
Tepper
Joel E
JE
McLeod
Howard L
HL
D014408:Biomarkers, Tumor / Q000097:blood*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000097:blood; D066246:ErbB Receptors / Q000097:blood; D006801:Humans; D019394:Ki-67 Antigen / Q000097:blood; D046228:Microarray Analysis; D020360:Neoadjuvant Therapy / Q000379:methods; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000097:blood; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D013940:Thymidylate Synthase / Q000097:blood; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000097:blood; D051028:bcl-2-Associated X Protein / Q000097:blood
C494826:BAX protein, human; D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D013940:Thymidylate Synthase; D066246:ErbB Receptors