Gastric Cancer
Gastric cancer is molecularly heterogeneous, and several of its subgroups — including Epstein–Barr virus associated and microsatellite unstable disease — have distinct biology that is relevant to how the disease is discussed.
Disease categories
Major disease categories
- Gastric adenocarcinoma
- Gastro-oesophageal junction tumours
- Diffuse-type gastric cancer
- Hereditary diffuse gastric cancer
Molecular
Molecular considerations
HER2 amplification, mismatch repair status, PD-L1 expression and Claudin 18.2 expression are among the markers most often assessed. CDH1 alterations are associated with diffuse-type disease and with a hereditary syndrome.
Markers commonly discussed in gastric cancer
- HER2
- PD-L1
- MMR / MSI
- Claudin 18.2
- EBV status
- CDH1
- FGFR2
Not exhaustive, and not every marker is assessed in every patient. Which of these is relevant depends on the individual case and should be discussed with the treating team.
Testing
Genomic testing considerations
HER2 assessment, mismatch repair testing and PD-L1 evaluation are commonly performed; broader panels are used in advanced disease.
Germline
Germline considerations
Germline CDH1 assessment is discussed in diffuse-type disease and where family history suggests hereditary diffuse gastric cancer.
Molecular monitoring
ctDNA and liquid biopsy considerations
ctDNA in gastric cancer is an area of active research, including for tracking HER2 status and molecular change during treatment.
Single-cell & computation
Single-cell and algorithmic approaches
In gastrointestinal and hepatobiliary disease, single-cell sequencing is used chiefly to characterise the tumour microenvironment and to resolve clonal structure in tumours that are heterogeneous between regions. Single-cell DNA analysis helps establish whether a RAS or driver alteration is clonal or subclonal, which bears directly on how much weight it should carry. Algorithm work here includes molecular residual disease detection from serial samples, mismatch repair classification from sequencing data, and pipelines that reconcile findings across multiple biopsy sites.
Decisions
Treatment decision questions
Questions worth raising with a treating team when a decision is being made:
- Is HER2 status established, and by which method?
- Has mismatch repair status been assessed?
- Is PD-L1 scored, and by which assay and scoring system?
Resistance
Resistance and recurrence questions
- Has HER2 status been reassessed after progression?
- Is there molecular evidence of a resistance mechanism?
Trials
Clinical trial considerations
Trial eligibility often depends on HER2, PD-L1 and Claudin 18.2 status.
When a precision oncology review may help
A review is most useful where the standard pathway has been exhausted or where the picture is more complicated than a protocol accounts for — rare presentations, treatment resistance, complex or apparently contradictory molecular findings, or a decision between several defensible options.
The output is a structured analysis and a set of questions for the treating team. It is not treatment, and it does not replace the treating oncologist.