TY - JOUR
T1 - Molecular characterization of gastric carcinoma
T2 - Therapeutic implications for biomarkers and targets
AU - Fonkoua, Lionel Kankeu
AU - Yee, Nelson S.
N1 - Publisher Copyright:
© 2018 by the authors.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - Palliative chemotherapy is the mainstay of treatment of advanced gastric carcinoma (GC). Monoclonal antibodies including trastuzumab, ramucirumab, and pembrolizumab have been shown to provide additional benefits. However, the clinical outcomes are often unpredictable and they can vary widely among patients. Currently, no biomarker is available for predicting treatment response in the individual patient except human epidermal growth factor receptor 2 (HER2) amplification and programmed death-ligand 1 (PD-L1) expression for effectiveness of trastuzumab and pembrolizumab, respectively. Multi-platform molecular analysis of cancer, including GC, may help identify predictive biomarkers to guide selection of therapeutic agents. Molecular classification of GC by The Cancer Genome Atlas Research Network and the Asian Cancer Research Group is expected to identify therapeutic targets and predictive biomarkers. Complementary to molecular characterization of GC is molecular profiling by expression analysis and genomic sequencing of tumor DNA. Initial analysis of patients with gastroesophageal carcinoma demonstrates that the ratio of progression-free survival (PFS) on molecular profile (MP)-based treatment to PFS on treatment prior to molecular profiling exceeds 1.3, suggesting the potential value of MP in guiding selection of individualized therapy. Future strategies aiming to integrate molecular classification and profiling of tumors with therapeutic agents for achieving the goal of personalized treatment of GC are indicated.
AB - Palliative chemotherapy is the mainstay of treatment of advanced gastric carcinoma (GC). Monoclonal antibodies including trastuzumab, ramucirumab, and pembrolizumab have been shown to provide additional benefits. However, the clinical outcomes are often unpredictable and they can vary widely among patients. Currently, no biomarker is available for predicting treatment response in the individual patient except human epidermal growth factor receptor 2 (HER2) amplification and programmed death-ligand 1 (PD-L1) expression for effectiveness of trastuzumab and pembrolizumab, respectively. Multi-platform molecular analysis of cancer, including GC, may help identify predictive biomarkers to guide selection of therapeutic agents. Molecular classification of GC by The Cancer Genome Atlas Research Network and the Asian Cancer Research Group is expected to identify therapeutic targets and predictive biomarkers. Complementary to molecular characterization of GC is molecular profiling by expression analysis and genomic sequencing of tumor DNA. Initial analysis of patients with gastroesophageal carcinoma demonstrates that the ratio of progression-free survival (PFS) on molecular profile (MP)-based treatment to PFS on treatment prior to molecular profiling exceeds 1.3, suggesting the potential value of MP in guiding selection of individualized therapy. Future strategies aiming to integrate molecular classification and profiling of tumors with therapeutic agents for achieving the goal of personalized treatment of GC are indicated.
UR - http://www.scopus.com/inward/record.url?scp=85051250286&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85051250286&partnerID=8YFLogxK
U2 - 10.3390/biomedicines6010032
DO - 10.3390/biomedicines6010032
M3 - Review article
C2 - 29522457
AN - SCOPUS:85051250286
SN - 2227-9059
VL - 6
JO - Biomedicines
JF - Biomedicines
IS - 1
M1 - 32
ER -