Here it is, ladies and gents: the big fat elephant in the room. The C-word. The ultimate monster.
Not only is cancer a plot device (we're all waiting for the dreadful moment when it kills Conor's mom), it's also a metaphor for change and loss—which Conor experiences in droves. In the scene in which Conor's grandma tells him he's got a home with her and Conor tells her he won't need one, she says, "She'll seem better tomorrow, but she won't be, Conor" (6.38). We see change and loss in two ways here: not only is Conor's life changing dramatically, his mom's condition changes from day to day. He never knows if today will be the day he loses her or not. Cancer is, in effect, jerking them all around.
The pit monster could be seen as cancer in creature form. Ness describes it as, "[…] the real nightmare monster, formed of cloud and ash and dark flames, but with real muscle, real strength, real red eyes that glared back and him and flashing teeth that would eat his mother alive" (28.42). When Conor tries and fails to pull his mom from the pit monster's grasp, he sees that cancer is more powerful than any human being. You can only hang on for so long before you're forced to deal with the loss that's staring you right in the face.
As his mom gets sicker, Conor's peers begin to bully and ostracize him: "When Conor started having that nightmare, that's when Harry noticed him, like a secret mark had been placed on him that only Harry could see" (3.8). Harry pays special attention to Conor for a while, hitting him and tripping him, but Conor's teachers start handling him with kid gloves, then ignoring him altogether: "Conor hadn't heard a word of his lessons in school, but the teachers hadn't told him off for his inattentiveness, skipping over him when they asked questions to the class" (18.33).
All this special treatment is a constant reminder to Conor that his mom is sick. This kid just can't catch a break, even at school when things should be normal. He's losing his mom, and he's lost his best friend Lily, because she's the one who told everyone about the cancer: "And then everyone knew. Everyone. Which changed the whole world in a single day" (4.36). The day he lost Lily was the day everything truly changed, but it didn't prepare him for the change and loss of losing his mom. It didn't prepare him for the constant changes of drugs that failed, staying with his grandma more and more often, and the varying day-to-day degrees of his mother's steadily worsening sickness.