Hold the world! New opportunities for targeted therapy HR+ / HER2− mBC
Summary. Modern oncomammology demonstrates a rapid transition from universal empirical treatment regimens to precision therapy based on detailed molecular genetic profiling of the tumor. Hormone receptor-positive, HER2-negative (HR+ / HER2−) locally advanced or metastatic breast cancer (mBC) is the most common molecular subtype, the treatment of which in the initial stages standardly involves a combination of endocrine therapy with cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i). However, the inevitable development of both primary and secondary endocrine resistance determines the urgent need of the oncology community to develop new effective targeted strategies for second-line treatment. This article, from the standpoint of evidence-based medicine, examines the molecular mechanisms of tumor resistance to hormonal effects due to hyperactivation of the intracellular PI3K / AKT signaling cascade, caused by alterations in the PIK3CA, AKT1 genes and disorders of the PTEN suppressor function. Based on the results of a large-scale international phase III clinical trial CAPItello-291, the pathogenetic feasibility of using a new selective pan-AKT inhibitor capivasertib (TRUQAP) in combination with fulvestrant is substantiated. It has been demonstrated that timely molecular genetic testing allows the oncologist to abandon the non-selective appointment of cytotoxic chemotherapy in favor of personalized treatment, providing patients with the opportunity for long-term individualized control of the disease under the slogan «TRUQAP. Hold the world!».
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