Molecular-targeted therapy toward precision medicine for gastrointestinal cancer: Current progress and challenges

Table 1 Clinic al trials of esophageal cancer classified on molecular targets

Signaling	Agents	Type of trial	Line of treatment	Phase	Results	Comments
EGFR
NCT00100945	Gefitinib	Single group, open-label	Second	II	Completed	Gefitinib
NCT01249352	Nimotuzumab	Randmized, open-label	First	II/III	Completed	Chemoradiation + nimotuzumab
NCT02591784	Nimotuzumab	Single group, open-label	First	II	Completed	Radiotherapy+ nimotuzumab
NCT01855854	Icotinib	Single group, open-label	Second	II	Completed	Icotinib in EGFR-positive EC
NCT02353936	Afatinib (target EGFR/HER2)	Single group, open-label	Second	II	Active, not-recruiting	Afatinib
NCT01522768	Afatinib (target EGFR/HER2)	Single group, open-label	Second	II	Active, not-recruiting	Afatinib ± paclitaxel
NCT01608022	Dacomitib	Single group, open-label	Third	II	Completed	Dacomitib
NCT03817567	SCT200	Single group, open-label	Third	I/II	Recruiting	SCT200
NCT03770988	Poziotinib (target EGFR/HER2/HER4)	Single group, open-label	Third	II	Not yet recruiting	Poziotinib
RAF
NCT00917462	Sorafenib (target VEGFR2/PDGFR/RET/RAF1)	Single group, open-label	Third	II	Completed26275293	Sorafenib
HER2
NCT01608022	Vizimpro	Single group, open-label	First	II	Completed	Vizimpro
NCT02120911	Pertuzumab	Single group, open-label	First	I/II	Completed	Chemoradation + Ttastumab + pertuzumab
FGFR
NCT03292250	Nintedanib	Non-randmized, open-label	Second	II	Recruiting	Nintedanib
NCT02699606	Erdafitinib	Single group, open label	Second	II	Recruiting	Erdafitinib
VEGFR
NCT02773524	Regorafenib	Randomized, triple	Third	III	Recruiting	Regorafenib
NCT03762534	Ramucirumab	Randomized, open label	Second	II	Recruiting	Ramucirumab + paclitaxel
NCT03542422	Apatinib (target VEGFR2/c-Kit/Src)	Single group, open label	First	II	Not yet recruiting	Apatinib
NCT03787251	Apatinib	Randomized, open label	Second	II	Not yet recruiting	Apatinib + chemotherapeutic drug
NCT04063638	Anlotinib (target VEGFR/FGFR/PDGFR)	Single group, open label	First	II	Recruiting	Anlotinib
PI3K
NCT03544905	CYH33	Single group, open label	Second	I	Recruting	CYH33
NCT03292250	BYL719	Non-randmized, open-label	Second	II	Recruting	BYL719
mTOR
NCT01490749	Everolimus	Single group, open label	First	I	Completed	Everolimus + FXELOX followed by radiation
PARP
NCT03995017	Rucaparib	Non-randomized, open label	Second	I/II	Recruting	Rucaparib + Ramucirumab
NCT03829345	Olaparib	Single group, open-label	Third	II	Recruting	Olaparib
ALK
NCT03917043	APG-2449 (target ALK/FAK/ROS1)	Sequential Assignment	Second	I	Recruting	APG-2449
Hedgehog
NCT02138929	Sonidegib	Single group, open label	Third	I	Active, not recruiting	Sonidegib + everolimus
DKK1
NCT02013154	DKN-01	Non-randomized, open label	Third	I	Active, not recruiting	DKN-01 + paclitaxel or pembrolizumab + chemotherapy
SHP2
NCT04000529	TNO155	Non-randomized, open label	Third	I	Recuruiting	TNO155 + spartalizumab + ribociclib
Cadherin
NCT02375958	PCA062 (target P-cadherin)	Single group, open label	Third	I	Completed	PCA062 in p-cadherin positive tumors

EC: Esophageal cancer; PI3K: Phosphoinositide 3-kinase; AKT: Protein kinase B; also known as PKB, mTOR: Mammalian target of rapamycin; MEK: Mitogen-activated protein kinase; EGFR: Epidermal growth factor receptor; HER2/3/4: Human epidermal growth factor 2/3/4; MAPK: Mitogenactivated protein kinase; STAT3: Signal transducer and activator of transcription 3; VEGF: Vascular endothelial growth factor; VEGFR: Vascular endothelial growth factor receptor; PDGFR: Platelet-derived growth factor receptor; FGFR: Eibroblast growth factor receptor; HGF: Hepatocyte growth factor; MET: Mesenchymal-epithelial transition factor; TEK: Tunica interna endothelial cell kinase; DDR: Discoidin domain receptor tyrosine kinase; MKNK/MAP: Kinase-interacting serine/Threonine protein kinase; FLT3: Fms-related tyrosine kinase 3; N.A.: Not applicable; MSS: Microsatellite stable; DKK1: Dickkopf-1; ALK: Anaplastic lymphoma kinase; PARP: Poly (ADP-ribose) polymerases.