Sortilin‐related receptor is a druggable therapeutic target in breast cancer

Abstract

In breast cancer, the currently approved anti-receptor tyrosine-protein kinase erbB-2 (HER2) therapies do not fully meet the expected clinical goals due to therapy resistance. Identifying alternative HER2-related therapeutic targets could offer a means to overcome these resistance mechanisms. We have previously demonstrated that an endosomal sorting protein, sortilin-related receptor (SorLA), regulates the traffic and signaling of HER2 and HER3, thus promoting resistance to HER2-targeted therapy in breast cancer. This study aims to assess the feasibility of targeting SorLA using a monoclonal antibody. Our results demonstrate that anti-SorLA antibody (SorLA ab) alters the resistance of breast cancer cells to HER2 monoclonal antibody trastuzumab in vitro and in ovo. We found that SorLA ab and trastuzumab combination therapy also inhibits tumor cell proliferation and tumor cell density in a mouse xenograft model of HER2-positive breast cancer. In addition, SorLA ab inhibits the proliferation of breast cancer patient-derived explant three-dimensional cultures. These results provide, for the first time, proof of principle that SorLA is a druggable target in breast cancer.

Targeting a broad spectrum of KRAS-mutant cancers by hyperactivation-induced cell death

“…Fertilised chicken eggs were incubated as previously described ( 57 ). Briefly, the eggs were washed, and the development was started by placing the eggs in a 37 °C incubator.…”

Experimental Tumor Induction and Evaluation of Its Treatment in the Chicken Embryo Chorioallantoic Membrane Model: A Systematic Review

“…The second phase consisted of questions about CAM methodology, results, discussion, and conclusions. The articles were classified according to the score obtained: low quality (score 0-5), medium quality (score 6-15), and high quality (score [16][17][18][19][20]. Following this quality study, 6 articles were excluded (Figure 1), and 74 articles were included and are analyzed in Tables 1-5.…”

Wszystko na swoim miejscu – rola receptorów VPS10P w komórkowej segregacji białek

“…Wniosek ten został potwierdzony w przeprowadzonych niezależnie badaniach in vivo z użyciem mysiego modelu nowotworu piersi. Zastosowanie terapii przeciwciałem monoklonalnym Trastuzumab, swoistym wobec receptora HER2, u myszy z rozwiniętym nowotworem, w połączeniu z przeciwciałem skierowanym przeciwko SorLA, powodowało znaczne obniżenie poziomu proliferacji komórek nowotworowych w porównaniu z myszami leczonymi jedynie Trastuzumabem [124]. Doświadczenia przeprowadzone in vitro wykazały, że także sortilina może stanowić jeden z komponentów terapii celowanej w walce z wysoce agresywnym typem nowotworu piersi -tzw.…”