Further, this body of work makes numerous clinically relevant observations for the treatment of patients with advanced ALM including that (a) CDK4 and P16INK4A status does not robustly predict ALM patient survival, (b) CDK4 pathway alterations do not robustly predict ALM sensitivity to CDK4i/6i, (c) CDK6 protein expression does not robustly predict ALM sensitivity to CDK4i/6i, and (d) genetic status (e.g., copy number variation) does not correlate with protein expression of CDK4 pathway nodes. Here, CDK6 is linked to acral lentiginous melanoma.