Aprea AB has presented preclinical data at the American Association for Cancer Research (AACR) meeting in San Diego, USA. The data reveals that Aprea's candidate drug APR-246, a compound that reactivates mutant p53, is able to resensitize ovarian cancer cells to platinum compounds and doxorubicin.
A Phase Ib/II study with APR-246 in relapsed platinum sensitive ovarian cancer is currently open for recruitment. Aprea is part of the Karolinska Development portfolio.
Platinum-based drugs are since decades used as first-line treatment for many solid tumors. Patients with ovarian cancer often respond well to platinum compounds, but many of these patients develop resistance to platinum and die of chemotherapy refractory disease.
The mechanisms underlying resistance are multifactorial, but two of the main causes are mutations in the tumor suppressor protein p53 and elevated intracellular glutathione levels.
The preclinical data presented shows that APR-246 not only reactivates mutant p53, but also decreases intracellular glutathione levels in a dose-dependent manner. This unique mechanism of action, targeting both mutant p53 and glutathione, is likely to account for the strong synergistic effects of APR-246 and platinum drugs as well as resensitization of ovarian cancer cells, which were observed in the study.
“The results provide a strong rationale for the clinical trial in intermediate platinum resistant ovarian cancer and suggest that treatment with APR-246 in combination with platinum-based chemotherapy could have a broad applicability in the treatment of drug resistant p53 mutant human tumors”, comments Mikael von Euler, CMO of Aprea.
The title of Aprea’s poster presentation at AACR was “APR-246, a clinical-stage mutant p53-reactivating compound, resensitizes ovarian cancer cells to platinum compounds and doxorubicin”. The full abstract (Abstract # 1801), is available on www.aacr.org.