Table 3.
Prioritized EGFR Resistance Mutations
| Compound | No. of Pred Mut (No. of All Mut)a | Rank 1 Resistance Hotspot (No. of Mut)b | Confirmed Clinical Resistance Mutants (Rank relP)c | Rank 2 Resistance Hotspot (No. of Mut)b | Confirmed Clinical Resistance Mutants (Rank relP) | Rank 3 Resistance Hotspot (No. of Mut)b | Confirmed Clinical Resistance Mutants (Rank relP) |
|---|---|---|---|---|---|---|---|
| Erlotinib | 34 (469) | G796 (9) | NRd | T790 (5) | T790M (2) (Pao et al., 2005) | L718 (3) L788 (3) T854 (3) |
NR |
| Gefitinib | 43 (487) | G796 (14) | G796A (3) (Uramoto et al., 2007) | T790 (6) | T790M (2) (Kobayashi et al., 2005, Pao et al., 2005) | T854 (4) | NR |
| Osimertinib | 38 (415) | G796 (14) | G796S (1) (Ou et al., 2017b) G796D (2) (Zheng et al., 2017) G796R (5) (Ou et al., 2017b) |
C797 (4) | C797R (3) (Ou et al., 2017b) | L718 (3) G719 (3) V726 (3) A743 (3) |
NR |
| Cetuximab | 65 (1,153) | G471 (15) | NR | G441 (12) | G441R (1) (Braig et al., 2015) | S418 (10) | NR |
| Panitumumab | 65 (1,207) | S418 (14) | NR | G441 (12) | G441R (1) (Braig et al., 2015) | G471 (8) | NR |
See also Table S4.
The gatekeeper mutation is underlined.
a
The number of mutants predicted to confer resistance (no. of pred mut) from the initial pool of possible mutants within 5 Å of the ligands (no. of all mut).
b
Resistance hotspots are identified and ranked according to the number of viable mutants (no. of mut) predicted for a residue.
c
The relP was calculated for all resistance hotspot mutations. Clinically observed resistance mutations and their rank according to relP (rank relP) are highlighted for each resistance hotspot.
d
NR, not reported––none of the predicted mutations are reported to confer resistance against the drug.