Figure 1 The Precision Medicine Biomarker Landscape
Fig. 1 | Six major biomarker domains converging on precision medicine. Click any satellite node to highlight its card below.
Figure 1 | Each node represents a major biomarker domain. Click to expand clinical detail.
Section 1 Biomarker Categories
Genomic Markers
DNA · RNA · Variants
Alterations in DNA sequence or gene expression correlating with disease state, prognosis, or treatment response.
BRCA1/2EGFRKRAS
TP53ALK fusionMSI-H
- Somatic mutations — acquired tumour variants driving oncogenesis (KRAS G12C in NSCLC; sotorasib)
- Germline variants — inherited mutations influencing hereditary risk (BRCA1/2 → PARP inhibitor eligibility)
- Copy number variations — HER2 amplification defines trastuzumab and T-DXd eligibility
- Gene fusions — BCR-ABL1 in CML; EML4-ALK in NSCLC amenable to targeted TKI therapy
- TMB & MSI — tumour mutational burden and microsatellite instability predict pembrolizumab response
Proteomic Markers
Protein · Expression · IHC
Protein-level biomarkers reflecting tumour biology, immune environment, and signalling pathway activity.
PD-L1HER2PSA
CA-125CEAKi-67
- PD-L1 expression — TPS ≥50% predicts pembrolizumab monotherapy benefit in NSCLC (KEYNOTE-024)
- HER2 overexpression — IHC 3+ / ISH amplified defines eligibility for trastuzumab, T-DM1, T-DXd
- ER/PR receptors — hormone receptor status dictates endocrine therapy strategy in breast cancer
- Serum oncoproteins — PSA, AFP, CA-125, CEA used for screening, staging, and monitoring
- Ki-67 proliferation index — prognostic in breast and neuroendocrine tumours; informs chemotherapy decisions
Epigenomic Markers
Methylation · Chromatin
Heritable gene regulation changes without DNA sequence alteration — methylation patterns and chromatin remodelling.
MGMTmiRNAlncRNA
5-hmCcfDNA methyl
- MGMT promoter methylation — silences DNA repair; predicts temozolomide benefit in glioblastoma
- Cell-free methylation — cfDNA methylome profiling enables multi-cancer early detection (Grail Galleri)
- miRNA signatures — circulating microRNA panels for lung, ovarian, and HCC early detection
- Chromatin accessibility — ATAC-seq identifies open chromatin revealing oncogenic transcription factor activity
- 5-hydroxymethylcytosine — tissue-specific 5-hmC cfDNA patterns as pan-cancer detection markers
Metabolomic Markers
Metabolites · Pathway Flux
Small-molecule metabolites reflecting altered biochemical pathways — the downstream functional readout of genomic changes.
2-HGLactateKynurenine
CeramideAcylcarnitines
- 2-Hydroxyglutarate (2-HG) — IDH1/2 oncometabolite; serum levels monitor ivosidenib response in AML
- Warburg metabolites — elevated lactate and altered glucose flux; FDG-PET exploits this phenotype
- Kynurenine pathway — IDO1-driven immunosuppressive metabolite; target for IO combination strategies
- Lipid remodelling — sphingolipid and ceramide profiles altered across multiple tumour types
- Urine metabolomics — non-invasive panels for bladder, prostate, and renal cancer detection
Liquid Biopsy
ctDNA · CTCs · Exosomes
Minimally invasive sampling of tumour-derived analytes in blood or urine — enabling real-time tumour monitoring.
ctDNACTCscfRNA
ExosomesMRD
- Circulating tumour DNA — plasma ddPCR/NGS for EGFR T790M, KRAS, ESR1 detection; guides 2nd-line therapy
- Circulating tumour cells — CellSearch CTCs provide prognostic value in mBC, mPC, and mCRC
- Minimal residual disease — ultra-sensitive ctDNA detects molecular recurrence months pre-radiological progression
- Tumour-educated platelets — RNA cargo encodes tumour-specific signatures; pan-cancer diagnostic potential
- Extracellular vesicles — exosomal miRNA and protein cargo for diagnosis and treatment monitoring
Imaging Biomarkers
Radiomics · PET · MRI
Quantitative imaging features and radiotracer uptake patterns providing non-invasive insight into tumour physiology.
SUVmaxADC mapPSMA-PET
RECISTRadiomics
- FDG-PET SUVmax — metabolic staging; Deauville score for lymphoma response assessment
- PSMA-PET/CT — PSMA receptor imaging transforming prostate cancer staging and theranostics (¹⁷⁷Lu-PSMA-617)
- DWI-MRI / ADC — diffusion restriction reflects cellularity; guides targeted biopsy in prostate cancer
- Radiomics & AI — high-dimensional CT/MRI texture features predict molecular subtypes without biopsy
- RECIST / iRECIST — standardised tumour measurement for objective response assessment in trials
Section 2 Clinical Importance
01
Right Drug, Right Patient
Biomarker-selected populations achieve dramatically higher response rates — EGFR-mutant NSCLC treated with osimertinib yields ~80% ORR vs ~30% in unselected cohorts.
02
Early Detection
Multi-cancer early detection assays using cfDNA methylome profiling can identify 50+ cancers at stage I–II when curative intent is achievable.
03
Resistance Monitoring
Serial ctDNA quantification identifies acquired resistance mutations (EGFR C797S, MET amplification) weeks before radiological progression.
04
Toxicity Avoidance
Pharmacogenomic markers — DPYD, UGT1A1, TPMT — predict life-threatening drug toxicities, enabling individualised dose optimisation.
05
Trial Enrichment
Biomarker-stratified basket and umbrella trials maximise statistical power and accelerate approval timelines for defined molecular subgroups.
06
Prognostic Stratification
Integrated genomic-proteomic models risk-stratify patients, sparing low-risk individuals from unnecessary chemotherapy intensity and toxicity burden.
Figure 2 The Precision Medicine Workflow
Fig. 2 | From sample acquisition to dynamic monitoring — the six-stage clinical precision medicine pipeline.
Step 01
Sample Acquisition
Tissue biopsy, liquid biopsy, or imaging. Pre-analytical quality is critical for downstream assay integrity.
Step 02
Molecular Profiling
NGS panel, WGS/WES, RNA-seq, IHC, FISH, or MS-based proteomics depending on the clinical question.
Step 03
Variant Interpretation
ACMG/AMP pathogenicity classification, OncoKB actionability tiering, TMB calculation.
Step 04
MTB Review
Molecular Tumour Board integrates findings with clinical context for evidence-based recommendations.
Step 05
Targeted Therapy
Matched agent, immunotherapy, or trial enrolment. Companion diagnostic co-development validates biomarker utility.
Step 06
Dynamic Monitoring
Serial ctDNA, imaging, and clinical markers track response, MRD, and emerging resistance mechanisms.