AZD3463 / AstraZeneca - LARVOL DELTA

Genomic amplification of MCL1 as a therapeutic target for osteosarcoma (AACR 2025) - "The treatment for OS that combines surgery with chemotherapy, which consists of a four-drug combination of doxorubicin (DOX), cisplatin (CDDP), high-dose methotrexate (MTX), and ifosfamide, was established in 1970s, and it is still used as a standard therapy...Additionally, the combination of MIK665 with IGF-1R inhibitors, including OSI906, AEW541, and AZD3463, induced synergistic cell death by overcoming drug tolerance conferred by the activation of IGF signaling in OS cells...Moreover, the combination therapy of AZD5991 with OSI906 also reduced tumor growth in the NOS-10 xenograft model. These results suggest that genomic amplification of MCL1 in the 1q21.2-3 region, observed in nearly half of OS patients, may act as a predictive biomarker for combination therapy with an Mcl-1 inhibitor and an IGF1-R inhibitor."

Oncology • Osteosarcoma • Sarcoma • Solid Tumor • IGF1 • NOS1 • PIP5K1A

Loss of heterozygosity of CYP2D6 enhances the sensitivity of hepatocellular carcinomas to talazoparib. (PubMed, EBioMedicine) - "Exploiting the loss of drug-metabolizing enzyme gene activity in tumor cells following loss of heterozygosity could present a promising therapeutic strategy for targeted cancer treatment."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor

Combination of AZD3463 and DZNep Prevents Bone Metastasis of Breast Cancer by Suppressing Akt Signaling. (PubMed, Front Pharmacol) - "Finally, intraperitoneal injection of DZNep and AZD3463 ameliorated tumor progression and protected against bone loss. In summary, DZNep combined with AZD3463 prevented skeletal complications and inhibited breast cancer progression by suppressing Akt signaling."

Journal • Breast Cancer • Oncology • Osteoporosis • Solid Tumor

Effects of rapamycin and AZD3463 combination on apoptosis, autophagy, and cell cycle for resistance control in breast cancer. (PubMed, Life Sci) - "In the combination of rapamycin with AZD3463, the expression of CDKN1B, PTEN, FOXO3, and APC genes increases, and the expression of PRKCB and PIK3CG genes decreases. Our results showed that the use of AZD-RAPA reduced the resistance of cancer cells to treatment and it leads cancer cells to apoptosis."

Journal • Breast Cancer • Oncology • Solid Tumor • ALK • CDKN1B • FOXO3 • IGF1R • PIK3CG • PTEN

Temozolomide treatment combined with AZD3463 shows synergistic effect in glioblastoma cells. (PubMed, Biochem Biophys Res Commun) - "TMZ and AZD3463 treatments, either alone or in combination, downregulated mRNA expression of genes in the PI3K/AKT signaling pathway. The combination of TMZ with AZD3463 may increase the efficacy of single TMZ treatment in GBM cells due to decreased expression of genes in the PI3K/AKT signaling pathway that is responsible for drug resistance and intratumoral heterogeneity."

Journal • Glioblastoma • Oncology • Solid Tumor

Combination of Salinomycin and AZD3463 Reveals Synergistic Effect on Reducing the Viability of T98G Glioblastoma Cells. (PubMed, Anticancer Agents Med Chem) - "Salinomycin, AZD3463, and their combination may inhibit proliferation and induce apoptosis in GBM cells due to decrease in expression levels of genes acting in both the canonical and non-canonical Wnt signaling pathways. The Wnt signaling pathway may be involved in the salinomycin-AZD3463 drug interaction."

Journal • Glioblastoma • Oncology • Solid Tumor

AZD3463, an IGF-1R inhibitor, suppresses breast cancer metastasis to bone via modulation of the PI3K-Akt pathway. (PubMed, Ann Transl Med) - "By using the MDA-MB-231BO cell line, which is the osteotropic metastatic variant of the human breast adenocarcinoma cell line MDA-MB-231, and an in vivo model of breast cancer metastasis to bone, the current study evaluated the effect of AZD3463, an IGF-1R inhibitor, used alone or in combination with zoledronic acid (ZA), on the regulation of IGF-1R associated signal pathway and treatment of bone metastases (BM). Mechanistic investigations indicated that the apoptosis-inducing activity of AZD3463 could be associated to its role in the activation of the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway. These findings suggested that AZD3463 could serve as a promising therapeutic molecule for treating BM in breast cancer patients, particularly when applied in conjunction with ZA or other antitumor agents."

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The ALK inhibitor AZD3463 effectively inhibits growth of sorafenib-resistant acute myeloid leukemia. (PubMed, Blood Cancer J) - No abstract available.

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