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Solid tumours are particularly responsive to immune checkpoint blockade therapies due to the genetic impairment of effector T cells and their ineffective trafficking to tumours. Here we show that the activated oncogenic tyrosine kinase 1 in Tyrosine 18 can phosphorylate CSK, improving CSK function and restricting T-cell activation. Overall, our report reveals an important component of ICB resistance and holds the possibility of expanding the scope of ICB therapy to tumors that are currently unresponsive.
Source link: https://doi.org/10.1038/s41467-022-34724-5
Patients with advanced prostate cancer can live longer and improve quality of life with next-generation antiandrogen drugs like enzalutamide and abiraterone. Signaling, especially Wnt5a, plays a vital role in prostate cancer progression and the induction of resistance to enzalutamide and abiraterone. In enzalutamide-resistant prostate cancer, we found that the Wnt5a/FZD2-mediated noncanonical Wnt pathway is overexpressed in this study. Signal transduction of Blocking Wnt has not only reduced the availability of the noncanonical Wnt signaling pathway, but it also reduced the production of constitutively activated androgen receptor and AR variants. BERA-Wnt5a siRNA siRNA's inhibition of Wnt5a expression by the BERA-Wnt5a siRNA also reduced tumor formation and improved enzalutamide therapy in vivo, according to investigators. These results show that the Wnt5a/FZD2 signal pathway is instrumental in promoting enzalutamide resistance, and that targeting this pathway by BERA-Wnt5a siRNA can be used as a potential treatment for advanced prostate cancer.
Source link: https://doi.org/10.1158/1535-7163.MCT-22-0216
Prostate cancer that recurs following androgen-deprivation therapy is termed castration-resistant, is incurable, and is characterized by the reactivation of androgen receptor signaling. Compared to androgen-dependent PC and benign tissue, human castration-resistant prostate cancer, a kinesin with unusual structural features, is overexpressed in human castration-resistant prostate cancer. Both in vitro and in vivo, stable expression of KIF20A in androgen-dependent PC cells accelerated CRPC by the activation of AR signaling in vitro and in vivo. These findings are the first to establish KIF20A as a source of CRPC progression through AR activation and as a promising therapeutic goal against CRPC.
Source link: https://doi.org/10.1038/s41388-022-02307-9
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