FAS/FAS ligand ratio: a marker of oxaliplatin-based intrinsic and acquired resistance in advanced colorectal cancer

Clin Cancer Res. 2005 Jul 1;11(13):4770-4. doi: 10.1158/1078-0432.CCR-04-2119.


Purpose: Oxaliplatin-5-fluorouracil combinations have increased responses in first-line therapy up to 40% in advanced colorectal cancer. Unfortunately, those patients who will respond are unknown and initially sensitive patients become rapidly resistant to current therapies. FAS (CD95) and FAS ligand (FASL; CD95L) have been implicated in chemosensitivity through leading to apoptosis in response to DNA-damaging drugs. Whereas the proapoptotic role of FAS and FASL is well characterized, the function of their soluble forms as predictors of chemosensitivity remains unknown.

Patients and methods: Blood samples were obtained from 68 patients with advanced colorectal cancer who received oxaliplatin-5-fluorouracil combinations in first-line therapy. Computed tomographic scans were done every 3 months and responses were evaluated by Response Evaluation Criteria in Solid Tumors criteria. ELISA soluble FAS and soluble FASL analysis were done before treatment and every 3 months until disease progression. Ratios between soluble FAS and soluble FASL were established and its values and variations through time were related to treatment responses.

Results: We found a significant increase in soluble FAS levels and a significant decrease in FASL at 3 months compared with baseline (13.2 versus 10.02 ng/mL; P=0.0001; 0.07 versus 0.14 ng/mL; P=0.007, respectively). A significant increase in the soluble FASL levels up to 9 months (fourth to fifth extractions; 0.26 ng/mL) of therapy compared with first to third extractions (0.11 ng/mL; P=0.003) was also found. A random effect regression statistical model determined that >1.2-fold increase in soluble FAS/soluble FASL ratio was a marker of chemosensitivity (P = 0.001).

Conclusions: These data strongly indicate that an increment of soluble FAS/soluble FASL ratio after treatment could be an excellent marker of chemosensitivity in colorectal cancer. On the other hand, a decreased ratio after treatment can be a predictor of chemoresistance despite an initial response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / blood*
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / pathology
  • Drug Resistance, Neoplasm
  • Enzyme-Linked Immunosorbent Assay
  • Fas Ligand Protein
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Male
  • Membrane Glycoproteins / blood*
  • Middle Aged
  • Multivariate Analysis
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Predictive Value of Tests
  • Regression Analysis
  • Tomography, X-Ray Computed
  • Treatment Outcome
  • Tumor Necrosis Factors / blood*
  • fas Receptor / blood*


  • Biomarkers, Tumor
  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Glycoproteins
  • Organoplatinum Compounds
  • Tumor Necrosis Factors
  • fas Receptor
  • Oxaliplatin
  • Fluorouracil