Cancer

Cell culture and mouse studies suggest inhibiting Hsp70 could help treat prostate cancer resistant to Xtandi enzalutamide and/or Zytiga abiraterone acetate. In human prostate cancer cell lines, high Hsp70 levels were associated with resistance to Xtandi and Zytiga. In two of the Xtandi- and Zytiga-resistant cell lines, two siRNAs targeting Hsp70 increased sensitivity to Xtandi and Zytiga compared with a non-targeting siRNA. Also in the cell lines, two Hsp70 inhibitor tool compounds decreased growth compared with no treatment and increased sensitivity to Xtandi and Zytiga compared with vehicle. In an Xtandi-resistant xenograft mouse model of prostate cancer, the Hsp70 inhibitors plus Xtandi decreased tumor growth and increased survival compared with Xtandi alone. In an Xtandi-resistant patient-derived xenograft (PDX) mouse model of prostate cancer, one of the Hsp70 inhibitors decreased tumor growth and increased survival. Next steps could include optimizing the two Hsp70 inhibitors.

Pfizer Inc. and Astellas Pharma Inc. market the androgen receptor antagonist Xtandi for prostate cancer...