Ejector seats would work for a challenger stage accident.
The first shuttle with only 2 pilots on board did have aircraft style ejector seats. The problem comes when you have a crew of 7 on two levels - you could have down/side-ward firing seats, as used on some B52 variants, but that compromises the heat shield.
But the most dangerous part of the flight is on the pad, a seat capable of firing you horizontally far enough to be clear of an explosion on the pad would be difficult - you would probably need the entire crew compartment to eject on it's own set of rockets - but this wouldn't work on landing, the other dangerous stage.
Then there is the added danger of the rest of the flight - when inside the pressure hull you have the rockets necessary to blow a 2ton escape pod 3-5km clear of a pad fire.
But the most dangerous part of the flight is on the pad, a seat capable of firing you horizontally far enough to be clear of an explosion on the pad would be difficult - you would probably need the entire crew compartment to eject on it's own set of rockets - but this wouldn't work on landing, the other dangerous stage. Then there is the added danger of the rest of the flight - when inside the pressure hull you have the rockets necessary to blow a 2ton escape pod 3-5km clear of a pad fire.