Unlocking New Avenues in Breast Cancer Treatment: The Synergy of Kinase Inhibitors and Immunotherapy

Abstract

Cancer is one of the world's most significant health problems today. Currently, breast cancer has globally surpassed lung cancer as the most commonly diagnosed cancer in women. In 2020, an estimated 2,261,419 new cases were diagnosed in women worldwide. Therefore, there is a need to understand the processes that can help us better treat this disease. In recent years, research in the fight against cancer has often been based on two treatment modalities. One of them is the use of protein kinase inhibitors, which have been instrumental in the development of new therapeutic strategies. Another crucial route is the use of immunotherapy, which has been touted as a great promise for cancer treatment. Protein kinase alterations can interfere with the effectiveness of other treatments, such as immunotherapy. In this review, we will analyze the role played by protein kinase alterations in breast cancer and their possible impact on the effectiveness of the response to immunotherapy treatments.

Keywords: antibody monoclonal; breast cancer; combination therapies; immunotherapy; inhibitor; protein kinase.

Figure 1

General information about protein kinases. Description of their activity and classification according to cellular location, activity, and catalytic domains. Adapted with permission from Reference [24]. Copyright 2019, copyright García-Aranda M, Redondo M.

Figure 2

Tyrosine kinase inhibitors and implicated receptors. The mechanism of action of combination therapy of kinase inhibitors with other drugs, as well as the receptors involved in different trials, is detailed here. Images were created using Biorender.com (accessed on 14 September 2023).

Figure 3

Mechanism of action of the different HER2 antibodies. (A,B) Monoclonal antibodies that are directed against epitopes present in the external domain of HER2 receptors. (C) Antibody–drug conjugates (ADCs): antibody directed to a target antigen; the payload, a cytotoxic agent; and a linker, which connects the antibody to the payload. (D) Bispecific antibodies. (E) A combination of ADCs and bispecific antibodies. The image was created using Biorender.com (accessed on 14 September 2023).

Figure 4

Anti-PD-1/PD-L1 with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Various trials are evaluating the combination of antibodies against PD-1/PD-L1 with CDK4/6 kinase inhibitors, along with other chemotherapy drugs. Image was created using Biorender.com. https://app.biorender.com/illustrations/6408b8a6a9e401e58f089c31 (accessed on 28 March 2023).