title: Molecular determinants of response to cisplatin-based neoadjuvant chemotherapy.
abstract: OBJECTIVE
  Neoadjuvant chemotherapy followed by cystectomy improves survival compared with surgery alone. To prevent overtreatment is of outmost importance to define molecular predictors of response for patient selection. We present the currently available data outlining a variety of potential markers to aid for a personalized decision-making process.
  
  
  RESULTS
  Apart from p53, other markers of cell cycle regulation and apoptosis such as p21WAF1/CIP1 (p21) gene, Bcl-2, mouse double minute-2 and pRB have also been related to survival. The clinical relevance of epidermal growth factor receptor and HER2 expression has also been investigated with no success. Regarding Ki67, overexpressing tumors may potentially benefit from neoadjuvant therapy and conversely overexpression of vascular endothelial growth factor and bFGF have been linked to resistance to cisplatin-induced apoptosis. The role of multidrug resistance gene 1 and excision repair cross-complementing rodent repair deficiency complementation group 1 supports that enhanced DNA repair in the tumor decreases the benefit of platinum-based treatment. A 20-gene expression model has shown to predict lymph node involvement, helping on decision-making. A gene expression profiling has been proposed as predictive for response to neoadjuvant chemotherapy.
  
  
  CONCLUSIONS
  Predictive markers will eventually aid in the selection of patients that most likely benefit from preoperative treatment. In the coming years, a panel of markers will become available to achieve the predicted goal.
authors.affiliation: Laboratoy Recerca IMIM, University Hospital del Mar, Barcelona, Spain. Joaquim_bellmunt@dfci.harvard.edu
authors.forename: Joaquim
authors.initials: J
authors.lastname: Bellmunt
authors.forename: Francesc
authors.initials: F
authors.lastname: Pons
authors.forename: Anna
authors.initials: A
authors.lastname: Orsola
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D015653:Cystectomy; D006801:Humans; D020360:Neoadjuvant Therapy; D018579:Patient Selection; D057285:Precision Medicine; D011237:Predictive Value of Tests; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000601:surgery
chemical_list: D014408:Biomarkers, Tumor; D002945:Cisplatin