TY - JOUR
T1 - Pharmacogenomics of genes involved in antifolate drug response and toxicity in osteosarcoma
AU - Hattinger, Claudia Maria
AU - Tavanti, Elisa
AU - Fanelli, Marilù
AU - Vella, Serena
AU - Picci, Piero
AU - Serra, Massimo
PY - 2017/3/4
Y1 - 2017/3/4
N2 - Introduction: Antifolates are structural analogs of folates, which have been used as antitumor drugs for more than 60 years. The antifolate drug most commonly used for treating human tumors is methotrexate (MTX), which is utilized widely in first-line treatment protocols of high-grade osteosarcoma (HGOS). In addition to MTX, two other antifolates, trimetrexate and pemetrexed, have been tested in clinical settings for second-line treatment of recurrent HGOS with patients unfortunately showing modest activity. Areas covered: There is clinical evidence which suggsest that, like other chemotherapeutic agents, not all HGOS patients are equally responsive to antifolates and do not have the same susceptibility to experience adverse drug-related toxicities. Here, we summarize the pharmacogenomic information reported so far for genes involved in antifolate metabolism and transport and in MTX-related toxicity in HGOS patients. Expert opinion: Identification and validation of genetic biomarkers that significantly impact clinical antifolate treatment response and related toxicity may provide the basis for a future treatment modulation based on the pharmacogenetic and pharmacogenomic features of HGOS patients.
AB - Introduction: Antifolates are structural analogs of folates, which have been used as antitumor drugs for more than 60 years. The antifolate drug most commonly used for treating human tumors is methotrexate (MTX), which is utilized widely in first-line treatment protocols of high-grade osteosarcoma (HGOS). In addition to MTX, two other antifolates, trimetrexate and pemetrexed, have been tested in clinical settings for second-line treatment of recurrent HGOS with patients unfortunately showing modest activity. Areas covered: There is clinical evidence which suggsest that, like other chemotherapeutic agents, not all HGOS patients are equally responsive to antifolates and do not have the same susceptibility to experience adverse drug-related toxicities. Here, we summarize the pharmacogenomic information reported so far for genes involved in antifolate metabolism and transport and in MTX-related toxicity in HGOS patients. Expert opinion: Identification and validation of genetic biomarkers that significantly impact clinical antifolate treatment response and related toxicity may provide the basis for a future treatment modulation based on the pharmacogenetic and pharmacogenomic features of HGOS patients.
KW - methotrexate
KW - Osteosarcoma
KW - pharmacogenetic
KW - pharmacogenomic
KW - toxicity
KW - treatment response
UR - http://www.scopus.com/inward/record.url?scp=85013229361&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85013229361&partnerID=8YFLogxK
U2 - 10.1080/17425255.2017.1246532
DO - 10.1080/17425255.2017.1246532
M3 - Review article
C2 - 27758143
AN - SCOPUS:85013229361
VL - 13
SP - 245
EP - 257
JO - Expert Opinion on Drug Metabolism and Toxicology
JF - Expert Opinion on Drug Metabolism and Toxicology
SN - 1742-5255
IS - 3
ER -