Molecular mechanisms targeting drug-resistance and metastasis in colorectal cancer: Updates and beyond

Table 1 Agents targeting epidermal growth factor receptors and downstream molecules under clinical investigation for the treatment of drug-resistant and metastatic colorectal cancer

Agent	Targeted molecule	Condition	Study phase	Clinical trial identifier
Erlotinib	EGFR	First-line treatment for mCRC	Phase III	NCT01229813
Futuximab/Modotuximab (Sym-004)	EGFR	mCRC	Phase II	NCT02083653
Gefitinib	EGFR	Refractory CRC	Phase I/II	NCT00242788
Afatinib	EGFR	Refractory mCRC	Phase II	NCT01919879
		Advanced CRC	Phase II	NCT00801294
		mCRC	Phase II	NCT01152437
Dabrafenib (GSK2118436)	BRAF	mCRC	Phase II	NCT03668431
		mCRC	Phase II	NCT03428126
BMS-908662	BRAF	K-RAS/BRAF-mutated CRC	Phase I/II	NCT01086267
Encorafenib	Wild-type and BRAF V600E	Previously untreated BRAF-mutant mCRC	Phase II	NCT03693170
Vemurafenib	Mutated BRAF V600E	BRAF V600E mutated advanced CRC	Phase II	NCT03727763
PX-866	PI3K	mCRC	Phase I/II	NCT01252628
Gedatolisib	PI3K/mTOR	KRAS/NRAS-wild-type mCRC	Phase II	NCT01925274
		mCRC	Phase I/II	NCT01937715
Temsirolimus CCI-770	mTOR	KRAS-mutated mCRC	Phase II	NCT00827684
		Cetuximab-refractory CRC	Phase I	NCT00593060
Everolimus (RAD001)	mTOR	mCRC	Phase II	NCT01387880
		mCRC	Phase I/II	NCT01058655
		Advanced mCRC	Phase I/II	NCT01139138
		Refractory mCRC	Phase I	NCT01154335
MK-2206	AKT	Advanced CRC	Phase II	NCT01333475
Napabucasin (BBI608)	STAT3	Previously treated mCRC	Phase III	NCT03522649
Cobimetinib	MAPK	mCRC	Phase III	NCT02788279
Selumetinib	MEK	mCRC	Phase II	NCT00514761
Binimetinib	MEK	Previously untreated BRAF-mutant mCRC	Phase II	NCT03693170
Neratinib	EGFR/HER2/4	KRAS/NRAS/BRAF/PIK3CA-wild-type mCRC	Phase II	NCT03457896
Sapitinib (AZD-8931)	EGFR/HER2/3	mCRC	Phase II	NCT01862003
Duligotuzumab (MEHD7945A)	EGFR/HER3	KRAS-mutated mCRC	Phase II	NCT01652482
Trastuzumab	HER2	First-line HER2-positive mCRC	Phase III	NCT05253651
Tucatinib	HER2	First-line HER2-positive mCRC	Phase III	NCT05253651
Disitamab Vedotin	HER2	HER2-positive advanced CRC	Phase II	NCT05493683
		HER2-expressing mCRC	Phase II	NCT05333809
Trastuzumab-emtansine	HER2	HER2-positive mCRC progressing after trastuzumab and lapatinib	Phase II	NCT03418558

EGFR: Epidermal growth factor receptor; mCRC: Metastatic colorectal cancer; PI3K: Phosphoinositide 3-kinases; mTOR: Mammalian target of rapamycin; STAT3: Signal transducer and activator of transcription 3; AKT: Protein kinase B; MAPK: Mitogen-activated protein kinases; MEK: Mitogen-activated extracellular signal-regulated kinase; HER2: Human epidermal growth factor receptor 2.