Table 2 Promising future biomarkers

HER2 loss

Loss of HER2 overexpression after anti-HER2 treatment

Predictive: secondary resistance to anti-HER2 agents

[102]

EGFR, MET, KRAS, ERBB3, CCNE1, CDK6, CCND1, FGFR2 and PIK3CA alterations, loss of PTEN

Secondary driver alterations (mutations/amplification) co-occurrent with HER2 amplification in GEA

Predictive: primary resistance to anti-HER2

Potential target for combined blockade

[98,99,100,101]

MYC, EGFR, FGFR2 and MET amplifications

Acquired alterations under anti-HER2 treatment pressure

Predictive: secondary resistance to anti-HER2 agents

Potential target for novel treatment strategies

[103, 104]

Liquid biopsy

Mutational analysis of circulating tumor DNA

Molecular profiling and identification of predictive mutations for targeted treatments at baseline

Dynamic monitoring of treatment response/disease progression

Early detection of secondary resistance

[111,112,113,114,115,116,117]

DNA methylation

Aberrant promoter DNA methylation in target genes

Diagnostic value

Negative prognostic value

Possible predictive value and role as novel treatment target

[118,119,120]

miRNA

Micro RNA: short noncoding single-stranded RNA molecules, with post-transcriptional regulatory functions

Diagnostic and prognostic value

Possible predictive value and role as novel treatment target

[124,125,126,127,128,129]

lncRNA

Long noncoding RNA: noncoding single-stranded RNA molecules, > 200 nucleotides, involved in cancer development and metastases

Possible diagnostic and prognostic value

Possible predictive value and role as novel treatment target

[125, 130,131,132]

PDX models

Patient-derived xenograft animal models with defined molecular signatures

Predictive: preclinical studies with targeted drugs

[133, 134]