Gene, genetics and genetic medicines in gastroenterology: Current status and its future

Table 11 Gastrointestinal and hepatopancreatic biliary disorders targeted therapy based on genetic testing[128-148]

Gene/pathway	Targeted drug(s)	Clinical status and trial setting	Ref.
KRAS G12C	Sotorasib, adagrasib (+ cetuximab)	Colorectal cancer, FDA approved	Ros et al[128]
EGFR (mAB)	Cetuximab, panitumumab, necitumumab	Colorectal cancer, gastric, FDA approved	Xie et al[129]
EGFR TKI	Erlotinib, gefitinib, afatinib, osimertinib, amivantamab	Colorectal cancer, gastric cancer, FDA approved	Corvaja et al[130]
VEGF	Bevacizumab, aflibercept	Colorectal cancer, gastric cancer	Mahaki et al[131]
BRAF V600E	Encorafenib, dabrafenib	Colorectal cancer, gastric cancer	Elez et al[132]
CLDN18.2	Zolbetuximab	Gastric/GEJ adenocarcinoma	Shitara et al[133]
NTRK fusion (NTRK1/NTRK2/NTRK3)	Larotrectinib, entrectinib	CRC, pancreatic, cholangiocarcinoma, gastric, others	Manea et al[134]
PD-1 (CD274 gene, checkpoint pathway)	Dostarlimab, camrelizumab1, nivolumab and pembrolizumab (keytruda)	Hepatocellular carcinoma, gastric and esophagogastric cancer	Abou-Alfa et al[135]
RET fusion	Selpercatinib, pralsetinib, avelumab	Rare GI/HPB tumors (cholangiocarcinoma, pancreatic)	Li et al[136]
FGFR2 fusion/rearrangement	Pemigatinib, futibatinib, infigratinib1	Intrahepatic cholangiocarcinoma	Hyung et al[137]
IDH1 mutation	Ivosidenib	Cholangiocarcinoma	Carosi et al[138]
BRCA1/BRCA2, PALB2 (HRD pathway)	Olaparib (PARP inhibitor)	Pancreatic adenocarcinoma (germline BRCA)	Alhusaini et al[139]
VEGFR, FGFR, PDGFR, RAF (angiogenesis/multikinase)	Sorafenib, lenvatinib, regorafenib, cabozantinib, pazopanib	Hepatocellular carcinoma	Kim[140]
APC mutation/COX2 pathway	Celecoxib (COX2 inhibitor)	FAP	Steinbach et al[141]
NR1H4 (FXR nuclear receptor)	Obeticholic acid	Primary biliary cholangitis	Floreani et al[142]
AGXT mutation (glyoxylate metabolism)	Lumasiran (RNAi against glycolate oxidase)	Primary hyperoxaluria type 1	Garrelfs et al[143]
SERPINA1 mutation (A1AT deficiency, liver disease)	Fazirsiran, ARO-AAT (RNAi)	Alpha-1 antitrypsin liver disease	Strnad et al[144]
ATP7B mutation	Chelators (penicillamine, trientine); zinc	Wilson disease
Anti-TNF agents	Infliximab, adalimumab	IBD	Feng et al[145]
IL-12/23 pathway	Ustekinumab (anti-IL-12/23)	IBD	Feng et al[145]
α4β7 integrin/cell trafficking	Vedolizumab (gut-specific anti-integrin)	IBD	Feng et al[145]
JAK-STAT pathway	Tofacitinib (pan-JAK), upadacitinib (JAK1)	IBD	Liu et al[146]
PD-L1 antibody	Durvalumab (imfinzi), atezolizumab, tislelizumab	GBC, HCC	Li et al[147]
MET amplification/overexpression	Foretinib1, cabozantinib (multi-target TKIs), glumetinib1	GBC, HCC, gastric, cholangiocarcinoma	Zhang et al[148]

¹Not Food and Drug Administration approved.

TKI: Tyrosine kinase inhibitors; PD-L1: Programmed death-ligand 1; PD-1: Programmed death-1; HRD: Homologous recombination deficiency; TNF: Tumor necrosis factor; COX2: Cyclooxygenase-2; IL: Interleukin; JAK-STAT: Janus kinase-signal transducer and activator of transcription; PARP: Poly (adenosine diphosphate-ribose) polymerase; RNAi: RNA interference; GEJ: Gastroesophageal junction; FDA: Food and Drug Administration; CRC: Colorectal cancer; GI: Gastrointestinal; HPB: Hepatopancreatic biliary; FAP: Familial adenomatous polyposis; IBD: Inflammatory bowel disease; GBC: Gallbladder cancer; HCC: Hepatocellular carcinoma.