AZD3514 / AstraZeneca - LARVOL DELTA

CTHRC1 expresses in cancer-associated fibroblasts and is associated with resistance to anti-androgen therapy in prostate cancer. (PubMed, Genes Genomics) - "As a potential molecular target of ADT resistance in prostate cancer, CTHRC1 provides a new promising molecular approach for the diagnosis and treatment of prostate cancer."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CAFs • CAV1 • CTGF • CTHRC1 • TGFB1

TET3 is expressed in prostate cancer tumor-associated macrophages and is associated with anti-androgen resistance. (PubMed, Clin Transl Oncol) - "The efficacy of ADT in prostate cancer is related to the expression of TET3 in TAMs, and TET3 may be a potential therapeutic target for coordinating ADT."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • TET3

AURKA inhibitor-induced PD-L1 upregulation impairs antitumor immune responses. (PubMed, Front Immunol) - "The expression of PD-L1 on SKBR3, MDA-MB-231, MCF7, 4T1, MC38 and B16 cells was evaluated by flow cytometry after treatment with six preclinical targeted drugs (ARN-509, AZD3514, Galeterone, Neratinib, MLN8237 and LGK974). When treated with MLN8237 in combination with anti-PD-L1 antibody, the volumes of tumor were significantly reduced and accompanied by increasing the infiltration of CD3+ and CD8+ T cells in colorectal cancer xenograft tumor model. Our data demonstrated that MLN8237 improved the effect of immunology-related therapy on tumor cells by interacting with anti-PD-L1 antibody, which contributed to producing creative sparks for exploring the possible solutions to overcoming drug resistance to tumor targeted therapy."

IO biomarker • Journal • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD8 • STAT3

Assessment of various continual reassessment method models for dose-escalation phase 1 oncology clinical trials: using real clinical data and simulation studies. (PubMed, BMC Cancer) - "Through simulation, the CRM generally outperformed the 3 + 3 method for the clinical and theoretical true dose-toxicity relationships. It was observed that accurate estimates of the true skeleton do not always outperform a generic skeleton, therefore the application of wide confidence intervals may enable a generic skeleton to be used. Further work is needed to determine the optimum skeleton."

Clinical data • Journal • P1 data • Oncology

Battling resistance mechanisms in antihormonal prostate cancer treatment: Novel agents and combinations. (PubMed) - "The wide variety in upcoming systemic agents underlines the molecular heterogeneity of castration-resistant PCa. This article reviews antihormonal therapy in PCa and resistance mechanisms and focuses on novel and upcoming agents currently in clinical testing."

Review • Biosimilar • Oncology • Prostate Cancer

Androgen receptor inhibitor enhances the anti-tumor effect of PARP inhibitor in breast cancer cells by modulating DNA damage response. (PubMed, Mol Cancer Ther) - "The study shows post-translational regulation of NKX3.1 via TOPORS up-regulation by AZD3514-induced ATM inactivation increased olaparib sensitivity in AR positive and TOPORS expressing breast cancer cells, and suggests the anti-tumor effect of AZD3514/olaparib co-treatment is caused by compromised DDR activity in breast cancer cell lines and in a xenograft model. These results provide a rationale for future clinical trials of olaparib/AR inhibitor combination treatment in breast cancer."

Journal • PARP Biomarker