Table 1.
PEA3 subfamily mediates chemotherapy resistance in cancer
| Major gene | Cancer type | PEA3 member | Drug | Mechanism |
|---|---|---|---|---|
| CIC | BRAF-mutated multiple myeloma | ETV4/5 | Dabrafenib, trametinib | Mediated by CIC inactivation, ETV4/5 contributes to dabrafenib and trametinib resistance in BRAF-mutated multiple myeloma cells. |
| CIC | T-ALL | ETV4 | Trametinib | CIC inactivation induces chemotherapy resistance to MAPK inhibition. ETV4 is the main downstream target of CIC in human T-ALL cells. |
| CIC | Pancreatic cancer | ETV1/4/5 | Trametinib | Deletion of ATXN1L induces chemotherapy resistance by reducing CIC protein levels and restoring expression of ETV1, ETV4, and ETV5. |
| CIC | NSCLC | ETV1 | Gefitinib | CIC suppresses the effects of EGFR inhibition by partially restoring the expression of ETV1. |
| CIC | Colorectal cancer | ETV5 | Cetuximab | ETV5 is a potential target to overcome cetuximab resistance. Knockdown of ETV5 increases cetuximab sensitivity in KRAS WT cells. |
| CIC | Ovarian cancer | ETV4/5 | Paclitaxel | ETV4 and ETV5 are upregulated by the miR-1307/CIC axis, which contributes to chemotherapy resistance. |
| COP1, DET1 | GIST | ETV1/4/5 | Imatinib, PD325901 | By stabilizing ETV1/ETV4/ETV5 protein, COP1 and DET1 loss results in chemotherapy resistance in GIST and melanoma. |
| Melanoma | ETV1/4/5 | Vemurafenib | ||
| IER3 | HCC | ETV4 | Sorafenib and cisplatin | ETV4 promotes sorafenib or cisplatin resistance in HCC by upregulating IER3, an oncogene related to chemotherapy resistance. |
| CDK6 | Melanoma | ETV5 | Vemurafenib | CDK6-mediated resistance to BRAF inhibition is collaboratively regulated by JUN and ETV5. |
| MDR1 | Gastric cancer | ETV4 | Vincristine | ETV4 upregulates MDR1 expression by binding to the promoter region of MDR1. |
T-ALL, T-cell lymphoblastic lymphoma; NSCLC, non-small-cell lung cancer; EGFR, epidermal growth factor receptor; GIST, gastrointestinal stromal tumor; HCC, hepatocellular carcinoma; WT, wild type; MDR1, multi-drug resistance protein 1.