Therapeutic antibodies are efficacious treatments with multiple mechanisms of action for eliminating tumor cells, including complement-dependent cytotoxicity (CDC), which leads to cell lysis. 2,3 Overexpression of membrane-bound complement regulatory proteins (mCRPs), such as CD46, CD55 and CD59, restricts CDC in tumors and decreases therapeutic antibodies efficacy. [4][5][6][7][8][9][10][11]

Breast cancer is one of the most aggressive diseases in women, responsible for thousands of deaths annually and millions of new diagnoses; its treatment presents multiple obstacles due to late diagnosis and the various mechanisms of tumor resistance. In breast cancer the membrane-bound complement regulatory proteins (mCRP) have been proposed as biomarkers of malignant cellular transformation. These are molecules capable of inhibiting therapeutic efficacy, from both antibodies and cytotoxic drugs. Therefore, these proteins are potential targets to increase therapeutic efficacy and avoid cancer progression. We will gather information about mCRP: (i) structural features; (ii) expression levels in breast cancer and relationship with prognosis; (iii) therapeutic resistance mechanisms; and (iv) strategies to down-regulate mCRP in both activity and expression.

Se ha propuesto a las proteínas reguladoras de complemento (mCRP) CD55, CD46 y CD59 como piezas clave en la resistencia terapéutica contra el cáncer. Las células tumorales que expresan las mCRP, además de obstaculizar la actividad terapéutica de trastuzumab, pertuzumab y sacituzumab-govitecan en cáncer de mama, pueden regular procesos biológicos que promueven la progresión tumoral. Esta revisión describe la estructura de las mCRP y analiza su expresión a partir de bases de datos transcriptómicos de pacientes con cáncer de mama; también recopila información de interacciones y señalización de las mCRP en células tumorales. Dado que estas mCRP son dianas relevantes, se describen diversas estrategias para su inhibición y regulación para incrementar la eficacia terapéutica y evitar la resistencia y progresión del cáncer.