PIK3CA and obesity due to melanocortin 4 receptor deficiency: Key components of metabolic syndrome, including obesity, insulin resistance, dyslipidemia, and chronic inflammation, promote tumor initiation and progression through alterations in insulin/IGF-1 signaling and major oncogenic pathways PI3K/AKT/mTOR and Ras/Raf/MEK/ERK, estrogen production, glucose metabolism reprogramming, and immune modulation.