Next-generation sequencing and molecular therapy

Cienne Morton; Debashis Sarker; Paul Ross

doi:10.7861/clinmed.2022-0514

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Table 1.

Selected targetable biomarkers in solid tumours

Biomarker	Alteration	Targeted therapies	Drug type	Tumour types with licensed indication
ALK	Rearrangement	Alectinib, brigatinib, lorlatinib, crizotinib	SM	NSCLC
BRAF V600E	Point mutation	Dabrafenib + trametinib (MEK inhibitor), vemurafenib + cobimetinib, encorafenib + binimetinib	SM	Melanoma, NSCLC, tumour agnostic (dabrafenib + trametinib)
EGFR	Deletion, point mutation	Erlotinib, gefitinib, afatinib, osimertinib	SM	NSCLC
FGFR2	Rearrangement	Pemigatinib, infigratinib^b	SM	BTC
FGFR3	Rearrangement	Erdafitinib	SM	Urothelial^b
FRα	Overexpression^a	Mirvetuximab soravtansine	ADC	Ovarian
HER2/ERBB2	Amplification, overexpression	Trastuzumab, pertuzumab	mAb	Breast, oesophagogastric (trastuzumab only)
		Tucatinib, neratinib, lapatinib	SM	Breast
		Trastuzumab deruxtecan	ADC	Breast, gastric/GOJ^b, NSCLC^b
HRD	Numerous alterations lead to this phenotype e.g. BRCA1 loss, ATM loss	PARP inhibitors e.g. olaparib, niraparib, rucaparib, talazoparib	SM	Ovarian, breast, prostate
IDH1	Point mutation	Ivosidenib	SM	BTC^b
KIT	Point mutation, deletion	Imatinib, sunitinib, avapritinib, regorafenib	SM	GIST
KRAS G12C	Point mutation	Sotorasib, adegrasib^b	SM	NSCLC
MET	Amplification, skip mutation	Capmatinib^b, tepotinib	SM	NSCLC
MSI-H	Point mutation, deletion, epigenetic	Immune checkpoint inhibitors eg nivolumab, pembrolizumab, ipilimumab,	mAb	Tumour-agnostic
Nectin-4	Overexpression^a	Enfortumab vedotin	ADC	Urothelial
NTRK	Rearrangement	Entrectinib, larotrectinib	SM	Agnostic
PDGFRA	Point mutation	Avapritinib	SM	GIST
PIK3CA	Point mutation	Alpelisib	SM	Breast
RET	Rearrangement	Selpercatinib, pralsetinib	SM	Thyroid, NSCLC
ROS1	Rearrangement	Crizotinib, entrectinib	SM	NSCLC
TF	Overexpression^a	Tisotumab vedotin	ADC	Cervical^b
Trop-2	Overexpression^a	Sacituzumab govitecan	ADC	Breast, urothelial^b
VHL	Point mutation, insertion/deletion, rearrangement, epigenetic	Belzutifan (blocks downstream HIF2α)	SM	RCC in Von Hippel Lindau disease

ADC = antibody–drug conjugate; BTC = biliary tract cancer; CRC = colorectal cancer; FRα = folate receptor alpha; GIST = gastrointestinal stromal tumour; HCC = hepatocellular carcinoma; HNSCC = head/neck squamous cell carcinoma; HRD = homologous recombination repair deficiency (genomic signature); mAb = monoclonal antibody; MSI-H = microsatellite instability-high (genomic signature); MMR = mismatch repair; NSCLC = non-small cell lung cancer; SM = small-molecule inhibitor; TF = tissue factor.
↵^aTargeted therapy approved regardless of biomarker status. Biomarker not routinely tested.
↵^bApproved by US Food and Drug Administration.