RB1 and obesity due to melanocortin 4 receptor deficiency: We speculate that the higher levels of circulating insulin in the Camkk2 WT mice, exacerbated during obesity, promote aberrant PI3K-AKT-mTOR signaling that potentially provides the missing third oncogenic piece to AVPCs previously driven by the other two genetic hallmarks of AVPC, RB1, and TP53 genetic alterations.