Lex Luthor’s Arrowverse debut came in Lex Luthor was introduced in Supergirl season 4, where he was transferred from prison to the Luthor Mansion on mercy furlough after suffering a stroke caused by his inoperable cancer.
In the source material, however, it was Lena who grew dangerously ill and this forced Lex to step up and try to cure her. Unfortunately, his attempt resulted in his sister becoming paralyzed. The villainous mastermind was unable to deal with his “failure” and hid her away at Lexcorp, telling others that she was dead instead of being honest about his attempts to save her. With Lena (played by Katie McGrath) a big part of the show, many expected to see this storyline play out, but it was switched up in a surprising way.
The Lex in the role of the ill Luthor sibling, he was suddenly dependant on his sister and this allowed Lena to be at the center of a huge storyline, setting the stage for her to prove herself by being the one to save him. She ultimately accomplished this by using the Harun-El she had been experimenting with, curing her brother and giving him superpowers in the process.
On that note, while it was important that Lena shone because she was a primary character, it was equally important to showcase how unflinchingly relentless Lex was when it came to achieving his goals. The storyline successfully pulled that off as it later revealed that Lex had intentionally given himself cancer so that he could trick his sister into curing him with the Harun-El. Moreover, knowing that he couldn’t risk her testing the experimental alien drug on him, he orchestrated the shooting of James Olsen (and forced a power outage during his life-saving surgery) so that she’d have no other choice than to test it on her ex-boyfriend. When it worked, he wasted little time in taking it, curing himself, and obtaining the powers he craved all along.
Lex put himself through all of this because he needed the Harun-El to cure the Red Daughter clone of Supergirl. That right there highlights how far he is willing to go to achieve his goals, because he didn’t do it out of comion, but out of necessity as it allowed him continue using her in his plan to bring down Supergirl and, ultimately, Superman. With Lex, the end justified the complex and life-threatening means - and that’s how you know the Arrowverse and Supergirl nailed Lex Luthor.