Yeah, the comparison to colonization doesn't really makes much sense to me. Using 16th century tech, you could expect to have a profitable trip pretty much every time you managed to come back alive, and you did not have to deal with bringing your own life support systems. With our technology, colonizing Mars is a much, much harder task, which has no foreseeable economic benefits for decades if not centuries.

Air, Water and Shelter are solved and field-proven. (eg. nuclear submarines can theoretically stay out for years, only limited by food)

Food is an interesting challenge, since we haven't done food production at scale beyond earth yet. Small scale experiments and applications seem promising though.

Full self-sustaining is not a requirement provided there is a supply chain. (And vice versa) . Of course: As self-self sustaining as possible as soon as possible would definitely be something to aim for.

The one company proposing to colonize mars in the near future would do so with a fleet of reusable spacecraft capable of 100-metric-tons to mars surface.

"Take three of everything" becomes a bit less of a problem in that kind of situation.

Within those constraints, the challenges are certainly still significant, but need not be insurmountable. Also said ship is -itself- not yet proven, so we'll have to wait and see.