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.