THE WARBURG EFFECT AND THE INSULIN/IGF-1 PATHWAY IN CANCER PROGRESSION: METABOLIC AND THERAPEUTIC PERSPECTIVES

Metabolic reprogramming is now recognized as a central hallmark of cancer. One of its most important features is the Warburg effect, a phenomenon in which tumor cells preferentially utilize aerobic glycolysis and convert glucose into lactate even in the presence of oxygen [1,4]. This metabolic adaptation supports rapid proliferation not only by generating ATP, but also by providing intermediates for nucleotide, amino acid, and lipid synthesis [1,4].

In parallel, the insulin/insulin-like growth factor-1 (IGF-1) signaling pathway has emerged as a major regulator of tumor growth, cell survival, and metabolic activity [2,3].

Hyperinsulinemia, increased IGF-1 bioavailability, and activation of IGF-1 receptor signaling can enhance downstream PI3K/AKT/mTOR signaling, which in turn promotes glucose uptake, glycolysis, and anabolic growth [2,3,5,6]. Evidence from experimental and translational studies suggests that the insulin/IGF-1 network does not merely accompany malignant growth, but actively strengthens the Warburg phenotype in metabolically responsive tumors [2,5,7].

This thesis reviews the biological relationship between the Warburg effect and insulin/IGF-1 signaling, explains their shared downstream mechanisms, and discusses their role in tumor progression and therapeutic targeting. The interaction between these processes helps explain why obesity, insulin resistance, and type 2 diabetes are associated with increased cancer risk and less favorable oncologic outcomes [2,3,6]. Understanding this crosstalk is highly important for modern oncology because it connects tumor cell biology with systemic metabolism and opens new perspectives for combined metabolic and targeted therapies [1-7].