What biomarkers should be tested for lung cancer?

Standard biomarker testing for lung cancer typically includes EGFR, ALK, ROS1, KRAS G12C, BRAF V600E, MET exon 14 skipping, RET, NTRK, PD-L1. Additional biomarkers may be tested depending on stage and clinical context.

When should lung cancer biomarker testing happen?

Biomarker testing should happen at diagnosis — before systemic therapy decisions. Many targeted therapies are only appropriate for specific biomarker profiles, so results are needed to choose the right first-line treatment.

Is germline genetic testing different from tumor biomarker testing?

Yes. Tumor (somatic) testing looks at the cancer itself to guide treatment. Germline testing, usually done on blood or saliva, looks at inherited mutations that may raise cancer risk for you and your blood relatives. Both can be important depending on the cancer type.

Biomarkers

Lung Cancer biomarkers — what to test

Non-small cell lung cancer (NSCLC) is one of the most mutation-driven cancers. Broad molecular testing is now standard at diagnosis for advanced/metastatic NSCLC and increasingly for earlier stages. The yield is high — many patients qualify for targeted therapy that outperforms chemotherapy. Small cell lung cancer (SCLC) has a much smaller biomarker panel.

Standard biomarkers

These are typically tested on every new diagnosis, or required before systemic therapy decisions, under current U.S. clinical guidelines.

EGFR

Standard

What it is: Epidermal Growth Factor Receptor mutations. Most common are exon 19 deletion and L858R point mutation. Less common: exon 20 insertion.

Why test: EGFR-mutated lung cancers respond to EGFR tyrosine kinase inhibitors with dramatic response rates. Higher prevalence in never-smokers and people of East Asian descent.

Therapies it unlocks:

Osimertinib (Tagrisso) — preferred first-line for common mutations
Amivantamab + lazertinib for exon 20
Mobocertinib for exon 20 (withdrawn 2023 — check current availability)

ALK

Standard

What it is: Anaplastic Lymphoma Kinase rearrangement (a gene fusion). Detected via IHC, FISH, or NGS.

Why test: ALK-rearranged lung cancers respond to ALK inhibitors with long durations of response.

Therapies it unlocks:

Alectinib (Alecensa) — often first-line
Brigatinib
Lorlatinib
Crizotinib

ROS1

Standard

What it is: ROS1 gene rearrangement. Rare (~1-2% of NSCLC).

Why test: Opens targeted therapy eligibility.

Therapies it unlocks:

Entrectinib
Repotrectinib
Crizotinib

KRAS G12C

Standard

What it is: A specific KRAS point mutation. Found in ~13% of NSCLC, more common in smokers.

Why test: Recently targetable after decades of being 'undruggable.' KRAS G12C inhibitors available.

Therapies it unlocks:

Sotorasib (Lumakras)
Adagrasib (Krazati)

BRAF V600E

Standard

What it is: A specific BRAF kinase mutation. Rare in lung cancer but highly actionable.

Why test: Opens eligibility for combination BRAF + MEK inhibitor therapy.

Therapies it unlocks:

Dabrafenib + trametinib
Encorafenib + binimetinib (under investigation/off-label)

MET exon 14 skipping

Standard

What it is: A splice mutation producing MET signaling dysregulation.

Why test: Targetable with MET inhibitors.

Therapies it unlocks:

Capmatinib (Tabrecta)
Tepotinib (Tepmetko)

RET

Standard

What it is: RET gene fusion. Rare in NSCLC but actionable.

Why test: Highly effective RET inhibitors available.

Therapies it unlocks:

Selpercatinib (Retevmo)
Pralsetinib (Gavreto)

NTRK

Standard

What it is: NTRK gene fusion. Very rare but tumor-agnostic targetable mutation.

Why test: Highly effective NTRK inhibitors across cancer types.

Therapies it unlocks:

Larotrectinib (Vitrakvi)
Entrectinib (Rozlytrek)

PD-L1

Standard

What it is: PD-L1 protein expression, reported as Tumor Proportion Score (TPS).

Why test: Guides first-line immunotherapy decisions. High PD-L1 favors pembrolizumab monotherapy; lower PD-L1 favors chemo + immunotherapy combinations.

Therapies it unlocks:

Pembrolizumab (Keytruda)
Nivolumab + ipilimumab
Atezolizumab
Durvalumab
Cemiplimab

Context-specific biomarkers

Tested depending on cancer stage, subtype, family history, or as part of broader NGS (next-generation sequencing) panels.

HER2

What it is: HER2 mutations or amplification in NSCLC (different from breast HER2 in clinical pattern).

Why test: Opens eligibility for HER2-targeted antibody-drug conjugate.

Therapies it unlocks:

Trastuzumab deruxtecan (Enhertu)

Tumor Mutational Burden (TMB)

What it is: Total count of mutations per megabase of tumor DNA.

Why test: TMB-High may predict immunotherapy response independent of PD-L1.

Therapies it unlocks:

Pembrolizumab (tumor-agnostic approval for TMB-H)

Questions to ask your oncologist

What biomarker testing are you doing on my tumor?
Are there any tests we are skipping that I should consider?
Will we wait for results before starting systemic therapy, or start something interim?
Is germline genetic testing appropriate for me, given my personal and family history?
If a biomarker test is indeterminate, what is the plan?

Next steps

FDA-approved lung cancer drugs →

See which FDA-approved drugs match each biomarker profile above.

Lung Cancer clinical trials →

Active recruiting trials, many biomarker-matched.

Biomarkers explained: full guide →

Deeper background on how biomarker testing works.

Germline genetic testing →

Different from tumor testing; addresses inherited cancer risk and family implications.

Genetic testing cost →

What germline and tumor molecular tests cost, and how insurance covers each.

BRCA test cost →

What patients pay in practice for BRCA1/2 testing and ACA preventive coverage rules.