Stress granules in colorectal cancer: Current knowledge and potential therapeutic applications

Table 2 Potential therapeutic approaches to impair stress granule function in cancer cells

Strategies	Target	Models	Known impact on SGs	Anticancer effect on CRC	Clinical trials for CRC (ID)
Targeting proteins involved in SG assembly
EGCG	G3BP1	Lung cancer[146]	Reduction of SG assembly	Yes[181]	NCT02891538; NCT02321969; NCT01239095
Resveratrol	G3BP1	CRC[145]	Unknown	Yes[145]	NCT00433576; NCT00920803
GAP161 peptide	G3BP1	CRC[43]	Unknown	Yes[43]	None
RK-33	DDX3	CRC[182]	Unknown	Yes[182]	None
Targeting G4DNA/RNA structures
EMICORON	G4DNA	CRC[147]	Unknown	Yes[147]	None
chANG	angiogenin	CRC[148]	Unknown	Yes[148]	None
(mAb), 26-2F	angiogenin	CRC[149]	Unknown	Yes[149]	None
Targeting AMPK/mTORC1 axis
Compound C	AMPK	Yeast[151] CRC[152]	Impairs SG assembly in yeast[151]	Yes[152]	None
Rapamycin	mTORC1	CRC[183]	Unknown	Yes[183]	NCT00409994; NCT03439462
Everolimus	mTORC1	Breast[16]	SG inhibition	Yes[184]	NCT01154335; NCT00419159; NCT01387880
Temsirolimus	mTORC1	CRC[185]	Unknown	Yes[185]	NCT00593060; NCT00827684; NCT01183663
Targeting HDACS/SIRTs
OSS_128167	SIRT6	Pancreas cancer[161]	Unknown	Unknown	No
A-452	HDAC6	CRC[158]	Unknown	Yes[158]	None
C1A	HDAC6	CRC[157]	Unknown	Yes[157]	None
ACY-1215	HDAC6	CRC[108]	Unknown	Yes[108]	None
MPT0G612	HDAC6	CRC[159]	Unknown	Yes[159]	None
Targeting SGs-associated RNA-binding proteins controlling cancer-related factors
MS-444	HuR	CRC[166]	Unknown	Yes[166]	None
DHTS	HuR	CRC[186]	Unknown	Yes[186]	None
Resveratrol	RBFOX2	CRC[101]	Unknown	Yes[101]	NCT00433576; NCT00920803
Targeting microtubules
Paclitaxel	Microtubules	Green monkey kidney fibroblasts (CV-1 cells)[153]	Promotes SG formation	Yes[187]	NCT00598247; NCT00024401; NCT00667641
Vinblastine	Microtubules	Green monkey kidney fibroblasts (CV-1 cells)[153]	Prevents SG assembly	Yes[188]	None

Several approaches can be used to efficiently reduce stress granule assembly and their oncogenic activities. This table provides some examples for each strategy. Some of them have been tested in colorectal cancers models and others have reached clinical trials (https://clinicaltrials.gov/). SG: Stress granule; CRC: Colorectal cancer.