CDK4/6 Inhibitor Resistance (oncology concept relevant to MHS)

When cancer cells are treated with CDK4/6 inhibitors, they eventually evolve resistance. One common mechanism is that cancer cells start relying more heavily on CDK2 instead of CDK4/6 — they "switch lanes" to keep dividing. Why this matters for MHS: The triple CDK2/4/6 inhibitor (culmerciclib) is interesting precisely because it blocks all three proteins at once, preventing the cancer cell from switching lanes. For MHS, this means a triple inhibitor might be more effective than a CDK2-only inhibitor, because the entire CDK family is involved in the microglial overactivation pathway, not just CDK2 alone.