Target-based agents in neoadjuvant treatment of liver metastases from colorectal cancer: secret weapons in anti-cancer war?
The therapeutic options for liver metastases of colorectal cancer mainly include surgical resection and palliative chemotherapy. More recently, the increased availability of new and more active cytotoxic drugs has increased the appeal of a combined treatment strategy, in which chemotherapy is administered before surgery. However, the efficacy of neoadjuvant chemotherapy of CRC liver metastases is limited by: (1) the persistence of micro metastatic foci that cannot be seen by conventional imaging techniques, placed either in other sites throughout the liver and/or in the site of the previous macroscopic metastasis that has undergone to clinical complete response; (2) the occurrence of escape mechanisms. The molecular basis regulating these processes are described and the first clinical attempts to overcome these mechanisms through the use of target-based agents are also reported. Finally, biological rationales to optimize the activity of these agents in neoadjuvant setting are discussed.
Marra
Monica
M
Department of Biochemistry and Biophysics, Second University of Naples, Naples, Italy.
Giudice
Aldo
A
Arra
Claudio
C
Vitale
Giovanni
G
Castiglioni
Sara
S
Nasti
Guglielmo
G
Lombardi
Angela
A
Ottaiano
Alessandro
A
Facchini
Gaetano
G
Iaffaioli
Rosario V
RV
Abbruzzese
Alberto
A
Caraglia
Michele
M
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D008954:Models, Biological; D020360:Neoadjuvant Therapy; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000068818:Cetuximab