Among the most widely used approaches, mTOR and PI3K inhibitors are used in synergy with tamoxifen, fulvestrant, trastuzumab, and lapatinib; more recent protocols also involve epigenetic drugs to interfere with the transcriptional regulation of BC signaling [i.e., human leukocyte antigen (HLA)-G is a non-classical MHC I molecule that protects the fetus from the mother’s IS but it is pathologically expressed in cancer; its levels can be lowered with a combinational strategy involving anti-HLA-G immunotherapy and specific DNA methyltransferase inhibitors] (7). The gene discussed is HLA-G; the disease is breast cancer.