Biomarkers & readouts

CPS counts every PD-L1-stained cell in the tumour, immune cells included, and divides by the number of tumour cells. Pembrolizumab labels use CPS 1 or CPS 10 as the gate in head and neck, stomach, oesophageal, cervical, ovarian and triple-negative breast cancer.

IHC 3+ means strong, complete membrane staining for HER2 in more than 10 percent of tumour cells. It is HER2-positive without needing a gene test and is the gate for trastuzumab, its combinations and antibody-drug conjugates in breast, stomach, biliary and, since 2024, any solid tumour.

V600E is the BRAF change that drives half of melanomas and many thyroid, bowel, lung and brain tumours. BRAF plus MEK inhibitors are approved for it in melanoma, lung, thyroid and, tumour-agnostically, any solid tumour; in bowel cancer it is treated with encorafenib and cetuximab.

An ALK fusion, usually EML4::ALK, is a swapped piece of chromosome 2 that turns the ALK kinase on permanently in about 4 percent of lung adenocarcinomas. Seven ALK inhibitors are approved for it, including alectinib after surgery.

dMMR means one of the four mismatch repair proteins is missing from the tumour cell nuclei on a stain. It is the tissue-level twin of MSI-high and opens checkpoint immunotherapy in endometrial, bowel and many other cancers.

An exon 19 deletion removes a few amino acids from the EGFR kinase and leaves it switched on. With L858R it makes up about 85 percent of EGFR-mutant lung cancer and is the classic gate for osimertinib and the other EGFR inhibitors.

A germline BRCA1 or BRCA2 variant is inherited and present in every cell, found by a blood test. It selects PARP inhibitors in breast, ovarian, pancreatic and prostate cancer and tells relatives they may carry it too.

KRAS G12C swaps glycine 12 for cysteine and was the first KRAS mutation a drug could grip. Sotorasib and adagrasib are approved for it in lung cancer, and with an EGFR antibody in bowel cancer.

MSI-high means the tumour's DNA has unstable repeat sequences, the footprint of failed mismatch repair. It is measured by PCR or sequencing, gives the same answer as dMMR in most tumours, and unlocks the same immunotherapies.

A ROS1 fusion drives about 1 to 2 percent of lung adenocarcinomas and behaves much like ALK. Crizotinib, entrectinib, repotrectinib and taletrectinib are approved for it.

Tumour BRCA testing finds BRCA1/2 mutations in the cancer itself, whether inherited or acquired; wider panels add other repair genes such as ATM and PALB2. Ovarian and prostate cancer labels accept the tumour result for PARP inhibitors.

ER status is whether the tumour's cells carry the oestrogen receptor, read by staining nuclei. One percent or more of stained nuclei is positive and means hormone-blocking treatment can work; 1 to 10 percent is 'low positive' and behaves more like negative.

FLT3-ITD is a duplicated stretch of the FLT3 receptor gene found in about a quarter of acute myeloid leukaemias; it makes relapse more likely and is treated with midostaurin, quizartinib or gilteritinib.

ISH counts copies of the HER2 gene in each tumour cell. A ratio of 2 or more against the chromosome 17 control, or 6 or more copies per cell, is amplified and HER2-positive whatever the protein stain showed.

IDH1 R132 mutations turn a metabolic enzyme into a producer of the oncometabolite 2-HG. They define lower-grade gliomas and occur in acute myeloid leukaemia and bile duct cancer, each with an approved IDH1 inhibitor.

The TC score is the percentage of tumour cells staining for PD-L1 on the SP263 or 28-8 assays. Atezolizumab uses 1 percent after lung surgery and 50 percent for first-line treatment alone; nivolumab with ipilimumab uses 1 percent in first-line lung cancer.

TPS is the share of tumour cells whose membrane stains for PD-L1, ignoring immune cells. In lung cancer it decides whether pembrolizumab or cemiplimab can be given alone: 1 percent opens the door, 50 percent is where single-agent treatment is strongest.

PIK3CA mutations in the helical and kinase domains are found in about 40 percent of hormone-receptor-positive breast cancers. Alpelisib, inavolisib and capivasertib are approved for tumours that carry them.

RET fusions drive 1 to 2 percent of lung cancers and some thyroid cancers; RET point mutations drive medullary thyroid cancer. Selpercatinib is approved for RET fusions in any solid tumour and for RET-mutant medullary thyroid cancer; pralsetinib for RET fusion lung cancer.

T315I is the gatekeeper mutation in the ABL1 kinase that defeats imatinib, dasatinib, nilotinib and bosutinib. Ponatinib and asciminib are the two drugs approved for it.

The BCR::ABL1 fusion is the Philadelphia chromosome that defines chronic myeloid leukaemia and some acute lymphoblastic leukaemia. Its transcript level in blood, on the international scale, is how response to tyrosine kinase inhibitors is measured and when treatment can be stopped.

L858R is a single letter change in exon 21 of EGFR that keeps the kinase active. It is the second commonest sensitising mutation and shares every EGFR inhibitor label with the exon 19 deletion.

ESR1 mutations arise in the oestrogen receptor's ligand-binding domain after aromatase inhibitor treatment, letting the receptor work without oestrogen. They are usually found in a blood test and select the oral SERDs elacestrant and imlunestrant.

FGFR2 fusions occur in 10 to 15 percent of intrahepatic bile duct cancers and almost nowhere else. Pemigatinib and futibatinib are approved for them after a first chemotherapy.

FLT3-TKD mutations are point changes in the kinase's activation loop, found in about 7 percent of acute myeloid leukaemias. Midostaurin and gilteritinib labels cover them; quizartinib's does not.

A HER2 mutation is a change in the gene's kinase domain, most often an exon 20 insertion, found in about 2 to 3 percent of lung adenocarcinomas. It is a different thing from HER2 amplification or overexpression, and it selects trastuzumab deruxtecan and, since 2025, zongertinib in lung cancer.

IHC 2+ is the in-between HER2 result: moderate staining that cannot be called positive or negative by eye, so the laboratory runs an ISH gene test. 2+ with amplification is HER2-positive; 2+ without it is HER2-low.

HLA-A*02:01 is the commonest tissue-type molecule in people of European descent and the one the first T-cell receptor therapies were built for. Tebentafusp and afamitresgene autoleucel work only in patients who carry it, so a blood HLA test comes before the tumour test.

HRD-positive means the tumour's genome carries the scars of failed double-strand break repair (or a BRCA mutation), measured as a genomic instability score. In ovarian cancer it selects niraparib, and olaparib with bevacizumab, as first-line maintenance.

IDH2 mutations at codons 140 and 172 do the same job as IDH1 R132, producing 2-HG. Enasidenib is approved for relapsed AML with them, and vorasidenib for grade 2 gliomas with either IDH gene mutated.

G12D is the commonest KRAS mutation, especially in pancreatic cancer, and has no approved drug yet. In bowel cancer any KRAS or NRAS mutation is a reason not to give EGFR antibodies, which is where the approvals sit.

MET exon 14 skipping is a splice-site change that lets the MET receptor escape degradation and keep signalling. It is found in 3 to 4 percent of lung cancers and is treated with capmatinib or tepotinib.

NPM1 mutations, found in about a third of adult acute myeloid leukaemias, misplace the nucleophosmin protein into the cytoplasm. They mean a better outlook without FLT3-ITD, a sensitive MRD marker, and since 2025 a targeted menin inhibitor.

An NTRK fusion joins one of three TRK kinase genes to a partner and drives cancers from infant fibrosarcoma to salivary and thyroid tumours, rare in common cancers but near-universal in a few rare ones. Larotrectinib, entrectinib and repotrectinib are approved for it regardless of tumour type.

PSMA-positive means prostate cancer deposits light up on a PSMA PET scan more than the liver does. It is the entry ticket for lutetium-177 PSMA therapy and the basis of the imaging that now stages most advanced prostate cancer.

PTEN can be lost by mutation or deletion (read by sequencing) or as absent protein on a stain. Both readouts select capivasertib: alterations in breast cancer, and protein deficiency in metastatic hormone-sensitive prostate cancer.

AKT1 E17K is a single hotspot mutation, in about 3 to 5 percent of hormone-receptor-positive breast cancers, that switches on the AKT kinase directly. It is one of the three alterations that qualify a patient for capivasertib.

A BRAF fusion joins another gene to the BRAF kinase, most often KIAA1549 in paediatric low-grade glioma. Tovorafenib is approved for children whose relapsed low-grade glioma carries a BRAF fusion or V600 mutation.

c-Met overexpression is a stain, not a gene change: strong (3+) membrane staining in at least half of tumour cells. It selects telisotuzumab vedotin, an antibody-drug conjugate, in previously treated non-squamous lung cancer.

CD19 is the B-cell surface protein that blinatumomab, CAR-T cells and several antibodies aim at. Blinatumomab's label requires CD19-positive leukaemia; the CAR-T labels assume it, and losing CD19 is the commonest way the disease escapes.

CD20 is the B-cell antigen rituximab made famous. Rituximab and obinutuzumab labels are written for CD20-positive lymphoma and leukaemia; the newer CD20 x CD3 bispecifics assume it.

CD22 is a second B-cell antigen, kept even when CD19 is lost. Inotuzumab ozogamicin is labelled for CD22-positive acute lymphoblastic leukaemia.

CD30 is the antigen of Hodgkin Reed-Sternberg cells and anaplastic large cell lymphoma. Brentuximab vedotin is labelled for Hodgkin lymphoma without a CD30 test and for peripheral T-cell lymphomas that express it.

CD33 is a myeloid antigen on the blasts of about 90 percent of acute myeloid leukaemias. Gemtuzumab ozogamicin's label requires CD33-positive disease.

Claudin 18.2 is a tight-junction protein exposed on stomach cancer cells. Zolbetuximab requires at least 75 percent of tumour cells to stain moderately or strongly, the strictest expression threshold in any current label.

A ctDNA MRD test looks for the tumour's own mutations in blood after surgery. Detection predicts relapse months before scans, and in 2026 the FDA approved Signatera as the companion test selecting bladder cancer patients for adjuvant atezolizumab.

Exon 20 insertions add amino acids after the C-helix of EGFR and make the kinase resistant to the usual EGFR tablets. They account for about a tenth of EGFR mutations and have their own drugs: amivantamab with chemotherapy and sunvozertinib.

T790M is the gatekeeper mutation that lung cancers acquire to escape first- and second-generation EGFR inhibitors. Finding it, in tissue or blood, is the historic gate for osimertinib after an earlier EGFR drug.

FGFR3 point mutations and TACC3 fusions drive about 15 to 20 percent of advanced bladder cancers. Erdafitinib is approved for tumours with these 'susceptible' alterations after one prior treatment.

Folate receptor alpha is a surface protein on most high-grade serous ovarian cancers. Mirvetuximab soravtansine requires FRα-positive disease, scored as at least 75 percent of cells with moderate or strong staining on the Ventana FOLR1 assay.

H3 K27M is a single change in a histone that defines diffuse midline glioma, including the brain-stem tumour DIPG. In 2025 dordaviprone became the first drug approved for tumours carrying it.

IHC 0 is no HER2 staining, or faint staining in 10 percent or fewer cells. It is HER2-negative, but the label now separates true zero from 'IHC 0 with membrane staining', the ultralow group that trastuzumab deruxtecan can treat in hormone-receptor-positive breast cancer.

IHC 1+ is faint, incomplete HER2 staining. It was called HER2-negative for twenty years; since 2022 it is the larger half of HER2-low, which trastuzumab deruxtecan treats in breast cancer.

HER2-low is not a new stain but a new reading of the old one: 1+ or 2+ without gene amplification. It covers about half of breast cancers and makes them eligible for trastuzumab deruxtecan.

HER2-ultralow is an IHC 0 result with a trace of membrane staining in a few cells. Since 2025, in hormone-receptor-positive breast cancer that has stopped responding to hormone therapy, it is enough for trastuzumab deruxtecan.

KIT D816V is the mutation behind almost every case of systemic mastocytosis. It makes the disease resistant to imatinib, and it is detected by a highly sensitive blood PCR; avapritinib treats the disease whether or not the mutation is confirmed.

The IC score measures how much of the tumour area is covered by PD-L1-stained immune cells rather than tumour cells. It belongs to the SP142 assay used with atezolizumab and is read differently from every other PD-L1 score.

PDGFRA D842V drives about 5 percent of gastrointestinal stromal tumours and is resistant to imatinib. Avapritinib is the approved drug for GISTs with PDGFRA exon 18 mutations including D842V.

PR status is read the same way as ER: 1 percent or more of nuclei staining is positive. It is measured alongside ER, adds to prognosis, and a tumour positive for either receptor counts as hormone-receptor-positive.

Somatostatin receptor-positive means a neuroendocrine tumour takes up a DOTATATE tracer on PET. It is the requirement for lutetium-177 dotatate and the marker that predicts response to octreotide and lanreotide.

TMB counts how many mutations a tumour carries per million DNA letters. Ten or more, measured by FoundationOne CDx, allows pembrolizumab for almost any solid tumour after other treatment has failed.

Loss of one copy each of chromosome arms 1p and 19q, together with an IDH mutation, defines oligodendroglioma in the WHO 2021 classification. It predicts a slower course and a good response to chemotherapy, and separates oligodendroglioma from astrocytoma.

AR-V7 is a shortened androgen receptor that lacks the part hormone drugs bind, so it stays active without testosterone. Found in circulating tumour cells, it predicts poor response to abiraterone and enzalutamide, but no label uses it yet.

B7-H3 is an immune checkpoint protein overexpressed on small-cell lung, prostate and many solid tumours. Ifinatamab deruxtecan is in phase 3 for small-cell lung cancer without an expression cut-off; nothing is approved.

BCMA is the plasma-cell antigen behind the myeloma bispecifics and CAR-T cells. None of their labels requires a BCMA test; expression is near-universal, and loss through BCMA gene deletion is a documented escape route.

Class II and III BRAF mutations sit outside codon 600 and signal as pairs (class II) or by leaning on RAS (class III). Approved BRAF inhibitors do not work on them, and no drug is yet approved for them; pan-RAF inhibitors are in trials.

CD38 is on almost every myeloma cell, so daratumumab and isatuximab are given without testing for it. The stain matters afterwards: CD38 falls after treatment and can confuse flow cytometry and blood typing.

CEACAM5 is the cell-surface form of the tumour marker CEA, high on many lung and bowel cancers. Tusamitamab ravtansine was tested in CEACAM5-high lung cancer but failed its phase 3 and no approval exists.

DLL3 sits on the surface of about 85 percent of small-cell lung cancers and almost no normal adult tissue. Tarlatamab is given without a DLL3 test.

FcRH5 is a third myeloma surface target after BCMA and GPRC5D. Cevostamab, the FcRH5 x CD3 bispecific, is in phase 3; no approval or threshold exists yet.

GPRC5D is a receptor on myeloma cells and in hair follicles, nails and taste buds. Talquetamab targets it without any test, and the side effects on skin, nails and taste follow from where it is expressed.

HER3 is a signalling partner of EGFR and HER2 present on most lung and breast cancers. Patritumab deruxtecan was studied in EGFR-mutant lung cancer without a HER3 threshold, and no approval exists.

Ki-67 is the percentage of tumour cells that are dividing. In neuroendocrine tumours it sets the grade; in breast cancer a 20 percent cut-off was briefly a condition of adjuvant abemaciclib, then dropped from the label in 2023.

MET amplification means extra copies of the MET gene, either as a primary driver in a few lung cancers or as the escape route after EGFR inhibitors. No label yet selects on it; trials define it by FISH ratio or copy number.

Methylation of the MGMT promoter switches off the repair enzyme that undoes temozolomide's damage. Methylated glioblastomas live longer on temozolomide; unmethylated ones gain little, and trials now use the result to spare or intensify chemotherapy.

MYCN amplification, more than four times the normal copy number of the gene on FISH, marks the most aggressive fifth of neuroblastomas and puts a child in the high-risk group whatever their age or stage. No drug targets it; it decides how much treatment is given.

Nectin-4 is expressed by almost every urothelial cancer, so enfortumab vedotin is given without a test. Nectin-4 amplification is being studied as a marker of especially strong response.

Tissue factor, the clotting trigger, is overexpressed on cervical and several other cancers. Tisotumab vedotin is labelled for cervical cancer without a tissue factor test.

TP53 mutation, or deletion of the 17p arm that carries the gene, is the single most common change in cancer and carries a worse outlook almost everywhere. In chronic lymphocytic leukaemia it decides treatment: chemotherapy is avoided and venetoclax's first approval was for del(17p) disease.

TROP2 is on the surface of most breast and lung cancers. Sacituzumab govitecan and datopotamab deruxtecan are given without measuring it; a computational TROP2 score is being tested as a selector in lung cancer.