Table 1 Summary of KRAS mutation cancers therapeutics
From: Targeting KRAS mutant cancers: from druggable therapy to drug resistance
Biomarker | Name | In vitro efficacy | In vivo efficacy | Ref. | |||
|---|---|---|---|---|---|---|---|
Tissue-Cell Line | IC50 (nM) | Dose (mg/kg) | Animal model | Inhibition% or Regression%a (Day) | |||
Act to directly inhibit KRAS | |||||||
 KRAS-G12C | ARS-1620 | Lung-H358 (KRAS-G12C) | 100 | 400 | Pancreas-MIA-PaCa2 (KRAS-G12C) | -52 (18) | [21] |
Pancreas-MIA PaCa-2 (KRAS-G12C) | 200 | 400 | Lung-H358 (KRAS-G12C) | -33 (27) | [21] | ||
MRTX849 | Lung-H2030 (KRAS-G12C) | 0.2 | 100 | Colorectal-CR6243 (KRAS-G12C) | -35 (20) | [43] | |
Lung-H358 (KRAS-G12C) | 2.5 | 100 | Lung-Calu-1 (KRAS-G12C) | -81 (22) | [43] | ||
Pancreas-MIA PaCa-2 (KRAS-G12C) | 29.6 | 100 | Pancreas-MIA PaCa-2 (KRAS-G12C) | -100 (19) | [43] | ||
Lung-SW1573 (KRAS-G12C) | 15.7 | 100 | Lung-LU65 (KRAS-G12C) | -97 (13) | [43] | ||
Lung-H1792 (KRAS-G12C) | 8.6 | 100 | Lung-H1373 (KRAS-G12C) | -95 (22) | [43] | ||
AMG510 | Pancreas-MIA PaCa-2 (KRAS-G12C) | 1 | 100 | Pancreas-MIA PaCa-2 (KRAS-G12C) | -56 (24) | [38] | |
Lung-H1373 (KRAS-G12C) | 5 | 100 | CRC-PDX (KRAS-G12C) | -69 (41) | [38] | ||
Lung-H2122 (KRAS-G12C) | 9 | 100 | CRC-CT- 26 (KRAS-G12C) | -59 (29) | [38] | ||
Lung-H358 (KRAS-G12C) | 3 | 100 | Lung-H358 (KRAS-G12C) | -50 (24) | [38] | ||
 KRAS-G12D | MRTX1133 | Stomach-AGS (KRAS-G12D) | 6 | 30 | Panc 04.03 (KRAS-G12D) | -70 (26) | [25] |
Targeted regulation of KRAS active protein | |||||||
 SOS1 | BAY-293 | Lung-H23 (KRAS-G12D) | 734 | – | – | – | [40] |
Colon-DLD1 (KRAS-G13D) | 640 | – | – | – | [40] | ||
BI-3406 | Lung-H23 (KRAS-G12D) | 9 | 50 | Pancreas-MIA PaCa-2 (KRAS-G12C) | 86 (22) | [41] | |
Lung-H358 (KRAS-G12C) | 24 | 50 | CRC-LoVo (KRAS-G13D) | 62 (23) | [41] | ||
Colon-DLD1 (KRAS-G13D) | 24 | 50 | CRC-B8032 (KRAS-G12C) | 27 (22) | [41] | ||
 SHP2 | SHP099 | Lung-H23 (KRAS-G12D) | 592 | 100 | Oesophagus-KYSE520 | 98 (14) | [44] |
Lung-H358 (KRAS-G12C) | 360 | – | – | – | [44] | ||
TNO155 | Lung-H3255 (EGFR-L858R) | 120 | 7.5 | Lung-H2030 (KRAS-G12C) | 43 (14) | [45] | |
Lung-HCC827 (EGFR-ex19del) | 700 | 7.5 | Esophageal cancer-KYSE410 (KRAS-G12C) | 87 (14) | [45] | ||
Inhibitors of KRAS upstream signaling pathway | |||||||
 EGFR | AZD9291 | Lung-H1975 (EGFR-L858R) | 25 | 10 | Lung-PC-9 (EGFR-ex19del) | -60 (14) | |
Lung-HCC827 (EGFR-ex19del) | > 250 | 10 | Lung-H1975 (EGFR-L858R/T790M) | -68 (14) | |||
JBJ-04-125-02 | B cell-Ba/F3 (EGFR-L858R) | 1000 | 100 | Lung-H1975 (EGFR-L858R/T790M) | -70 (35) | [48] | |
Inhibitors of KRAS downstream signaling pathway | |||||||
 MEK1/2 | GSK112021 | Pancreas-BXPC-3 (P53-mutant) | 10 | 0.3 | PDX-738 | -20 (14) | [49] |
 ERK1/2 | BVD-523 | Pancreas-MIA PaCa-2 (KRAS-G12C) | 500 | 100 | CRC-Colo205 (BRAF-V600E) | -100 (14) | [50] |
Chromoma-A375 (BRAF-V600E) | 500 | 100 | Chromoma-A375 (BRAF-V600E) | -100 (18) | [50] | ||
 BRAF | BGB283 | Chromoma-A375 (BRAF-V600E) | 64 | 5 | Colon-HT29 (BRAF-V600E) | 75 (22) | [51] |
Colon-HT29 (BRAF-V600E) | 50 | 10 | Colon-Colo205 (BRAF-V600E) | > 100 (15) | [51] | ||
 p110α | BYL719 | Medulloblastoma–DAOY (PIK3R1-mutant) | 5650 | 25 | Breast-MCF7 (PIK3CA-mutant) | -10 (21) | |
 AKT | MK2206 | Liver-Huh7 | 3100 | 100 | Pancreas-BT-474 (HER2-amplified) | 70 (28) | [54] |
 mTOR | RAD001 | Lymph-U937 | 20 | – | – | – | [55] |
OSI-027 | T cell-Jurkat | 300 | 65 | CRC-GEO | 100 (12) | ||
Degradation agent of KRAS | |||||||
 KRAS-G12C | LC-2 | Lung-SW1573 (KRAS-G12C) | 760 | – | – | – | [58] |
Lung-H23 (KRAS-G12C) | 250 | – | – | – | [58] | ||
Small interfering RNA therapies | |||||||
 KRAS mRNA | AZD4785 | Epidermal carcinoma-A431 | 10 | 50 | Lung-NCI-H358 | 55 (28) | [59] |