Table 2.
Observed alterations leading to GDP-KRASG12C inhibitor resistance for all indications.
| Gene | Mutation | Context of the alteration | Observing studies (PMID) |
|---|---|---|---|
| KRAS | A146V | Preclinical | 26841430 |
| A59G/S/T | Preclinical | 26841430; 33971321; 35471904 | |
| C12F | Preclinical | 35471904 | |
| D69P | Preclinical | 35471904 | |
| D92R | Preclinical | 35471904 | |
| F156L | Preclinical | 35471904 | |
| G12C AMP** | Clinical | 34161704 | |
| G12R/V/W | Clinical | 34161704; 33824136 | |
| G13D/E | G13D: preclinical and clinical; G13E: preclinical | 33824136; 34161704; 33971321; 35471904 | |
| H95D/N/R/Q/V | H95D/R: preclinical and clinical; H95Q: clinical; H95N/V: Preclinical | 35471904; 34161704 | |
| M72I | Preclinical | 33971321; 35471904 | |
| N116H | Preclinical | 26841430 | |
| Q61H/L | Q61L: preclinical; Q61H: clinical | 26841430; 33971321; 34161704 | |
| Q99F/L/W | Preclinical | 35471904; 33971321 | |
| R68L/M/S | R68L/M: preclinical; R68S: Preclinical and clinical | 33971321; 35471904; 34161704 | |
| S65W | Preclinical | 35471904 | |
| T58I | Preclinical | 35471904 | |
| V8A/E/L | Preclinical | 33971321; 35471904 | |
| V9Y | Preclinical | 35471904 | |
| Y40A | Preclinical | 26841430 | |
| Y64A | Preclinical | 26841430 | |
| Y96C/D/H/S | Y96C: preclinical and clinical; Y96D: clinical; Y96H/S: preclinical | 35471904; 34161704; 33824136; 33971321 | |
| AKAP9-BRAF | Fusion | Clinical | 34161704 |
| BRAF | V600E | Clinical | 34161704; 33824136 |
| CCDC6-RET | Fusion | Clinical | 34161704 |
| EGFR | A289V | Clinical | 34161704 |
| EML4-ALK | Fusion | Clinical | 34161704 |
| ERBB2 | Gain | Clinical | 34715459 |
| FGFR3-TACC3 | Fusion | Clinical | 34161704 |
| MAP2K1 | E102_I103del | Clinical | 34161704; 33824136 |
| I99_K104del | Clinical | 34161704 | |
| K57N/T | Clinical | 34161704; 33824136 | |
| Q56P | Clinical | 33824136 | |
| MET | AMP** | Preclinical and clinical | 34161704; 34365406 |
| NF1 | R2637* | Clinical | 34161704 |
| NRAS | Q61K/L/R | Clinical | 34161704; 33824136 |
| NRF1-BRAF | Fusion | Clinical | 34161704 |
| PIK3CA | H1047R | Clinical | 34161704 |
| PIK3R1 | S361fs | Clinical | 34161704 |
| PTEN | G209V | Clinical | 34161704 |
| N48K | Clinical | 34161704 | |
| RAF1-CCDC176 | Fusion | Clinical | 34161704 |
| RAF1-TRAK1 | Fusion | Clinical | 34161704 |
| RET | M918T | Clinical | 34161704 |
| RIT1 | P128L | Clinical | 34161704 |
| TP53 | F338fs | Clinical | 33824136 |
*
Nonsense mutation.
**
Amplification (AMP).