Overcoming Resistance to Therapies Targeting the MAPK Pathway in BRAF-Mutated Tumours

Table 1

Summary pharmacological interventions for BRAFV600E mutated cancers^✝.

Compound	Target	Pathway	Cancer type
Vemurafenib	BRAF	MAPK	CRC/G/M/T
Dabrafenib	BRAF	MAPK	CRC/M
Encorabenib	BRAF	MAPK	CRC/M
Trametinib	MEK	MAPK	CRC/M/PDA
Binimetinib	MEK	MAPK	M
Navitoclax	BCL-2/BCL-XL/BCLW	BH3 mimetic	M/T
ABT-737	BCL-2	BH3 mimetic	M
A-1210477	MCL-1	BH3 mimetic	M
Compound 1^+	SH2	STAT3	M
Hydroxychloroquine	Unknown	Autophagy	CRC/M/PDA
Lys05	Lysosome	Lysosomal autophagy	M
Chloroquine	Unknown	Autophagy	CRC/M/PDA
Temozolomide	DNA	DNA replication	M
KP1339/IT-139	GRP78	ER homeostasis	MT
GSK2606414	PERK	UPR^#	M
A443654.3	AKT	PI3K/AKT/mTOR	CC
MK2206	AKT	PI3K/AKT/mTOR	CRC
LY294002	PI3K	P3K/AKT/mTOR	CRC
GDC0941	PI3K	P3K/AKT/mTOR	CRC
PPP^++	IGF-1R	PI3K/AKT/mTOR	M
Iso-orientin	Unknown	PI3K/AKT/Mitochondria	HBC
TM^+++	Copper	Angiogenesis/inflammation	CRC
Ibuprofen	COX1/2	NSAID^##	MT
Naproxen	COX1/2	NSAID^##	MT
Celecoxib	COX-2	NSAID^##	SCC
Etomoxir	CPT1A	Lipid oxidation	M/P
Phenformin	AMPK	Metabolic regulator	M
β-sitosterol	Complex I	ETC^###	M
SR4	Proton uncoupler	Mitochondria	M
Niclosamide	Proton uncoupler	Mitochondria	M

CC = cholangiocarcinoma; CRC = colorectal carcinoma; G = glioma; HBC = hepatoblastoma cancer; M = melanoma; MT = multiple tumours;  = prostate; PDA = pancreatic ductal adenocarcinoma; PST = panel of solid tumours; SCC = squamous cell carcinoma; T = thyroid. ⁺Compound 1 = quinoxaline-2,3-diylbis (methylene) dicarbamimidoselenoate dihydrobromide. ⁺⁺PPP = cyclolignan propodophyllin. ⁺⁺TM = tetrathiomolybdate. ^#UPR = unfolded protein response. ^##NSAID = nonsteroidal anti-inflammatory. ^###ETC = electron transport chain. ^✝This is not a comprehensive list of compounds that target alternative mechanisms of BRAFi resistance and covers therapies that are referenced in this review.