GRB2 and breast carcinoma: Recently, we discovered a HCAR1 signaling cascade, where TME lactate secreted from breast cancer cells triggered cellular HCAR1 association with the PI3K and RAS signaling pathway components, such as growth factor receptor-bound protein 2 (GRB2), SOS Ras/Rac guanine nucleotide exchange factor 1 (SOS1), Kirsten rat sarcoma viral oncogene homologue (KRAS), GRB2-associated binding protein 1 (GAB1), and PI3K, for the activation of the oncogenic RAS and PI3K signaling pathways [10] (Figure 4).