Molecular predictive markers in tumors of the gastrointestinal tract

Table 1 Overall gene mutation frequency in each molecular signaling pathway

Biologic pathway	Frequency of mutation in genes involved in each pathway	Therapies that target the pathway
Beta-catenin/WNT signaling	75%	FZD, GSK inhibitors
Cell cycle control	68%	CDK, CDK1, CDK2, CDK4/6 inhibitors
Receptor tyrosine kinase/growth factor signaling	67%	Therapeutic antibodies/tyrosine kinase inhibitors
MAP kinase signaling	61%	BRAF, ERK, MEK AND SRC inhibitors
PI3K/AKT1/MTOR	52%	Allosteric mTORC1 inhibitors/mTORC1/2 catalytic inhibitors
DNA damage/repair	48%	PARP INHIBITORS
TGFbeta signaling	37%	TGFBR1 inhibitors
Chromatin remodeling/DNA methylation	32%	DNMT inhibitors, Histone deactylase
Immune checkpoints	26%	Anti-CTLA4 antibodies, anti-PD-1 antibodies, Anti-PD-L1 antibodies, Immunotherapies
JAK/STAT signaling	23%	JAK inhibitors
Hedgehog signaling	12%	SMO inhibitors

The information concerning therapies that target each molecular pathway was retrieved for MyCancer Genome Site (Available from: URL: http//http://www.mycancergenome.org/).

Table 2 Gene mutations identified in ctDNA of patients with tumors of the gastrointestinal tract and their correlation with possible clinical implications

Gene	Mutation type	Tumor type	Possible clinical implications	Ref.
KRAS/NRAS	Point mutation/amplification	Colorectal/pancreatic cancer	Resistance to anti-EGFR therapy/sensitivity to MEK inhibitors	[88-90]
BRAF	Point mutation	Colorectal cancer	Resistance to anti-EGFR therapy/sensitivity to MEK inhibitors	[88,91]
MET	Amplification/alteration	Colorectal/esophageal cancer	Resistance to anti-EGFR therapy/sensitivity to MEK inhibitors	[92-94]
HER2	Amplification	Colorectal/gastric cancer	Resistance to anti-EGFR therapy/sensitivity to Anti HER2 inhibitors	[95,96]
EGFR	Point mutation	Colorectal/pancreatic cancer	Panitumumab	[97,98]
PIK3CA	Point mutation	Colorectal/pancreatic cancer	mTOR inhibitor	[89]
Ckit	Point mutations	GISTS	Imatinib or dose escalation or alternative TKIs	[99,100]
PDGFRA	Point mutations	GISTS	Imatinib or dose escalation or alternative TKIs	[99,100]

TKI: Tyrosine kinase inhibitors; GIST: Gastrointestinal stromal tumors; EGFR: Epidermal growth factor receptor; mTOR: Mechanistic target of rapamycin.