Effective Therapy of Hepatocellular Carcinoma with the Combination of Sorafenib and a Glucose Analog
TS-037248 — A novel therapeutic strategy to sensitize Hepatocellular Carcinoma tumors to a multikinase inhibitor for advanced stage treatment.
Hepatocellular carcinoma (HCC) kills nearly all patients within a year of diagnosis, and results in between 250,000 and one million deaths globally per year. In the US, incidences of HCC have nearly tripled in the past 30 years and currently remain one of the fastest growing causes of cancer-relat…
Hepatocellular carcinoma (HCC) kills nearly all patients within a year of diagnosis, and results in between 250,000 and one million deaths globally per year. In the US, incidences of HCC have nearly tripled in the past 30 years and currently remain one of the fastest growing causes of cancer-related deaths (Goossens, Sun et al. 2015). Long-term patient prognosis is extremely poor and treatment options are limited. Currently, sorafenib is the only FDA-approved systemic therapy for advanced HCC in the United States, but patient development of sorafenib resistance is commonly observed (Yegin, Oymaci et al. 2016), underscoring the need for new and effective therapy against this deadly disease. Due to the time and cost associated with new drug discovery, repurposing currently approved drugs for use against HCC could be a more rapid and cost-effective approach to deliver treatment options for patients currently battling the disease.
Inventors at the Ohio State University led by Dr. Tasneem Motiwala have developed a therapy based on the use of fostamatinib, either alone or in combination with sorafenib. Drug repurposing analysis identified fostamatinib as a candidate that could reverse the gene expression signature of sorafenib resistant liver cancer cell line. Fostamatinib is also effective against sorafenib-sensitive liver cancer cell lines.
Although fostamatinib has not previously been identified as an effective treatment for HCC, it has been included in numerous clinical trials to determine safety and efficacy for other uses. The results of those trials, representing over 5,600 patients, demonstrated a low rate of adverse events (≃ 5%), indicating promise for future inclusion as a combinatorial therapy in human patients with HCC.
- Oncology treatments
- Combination therapies
- Reduction in time and cost of traditional drug discovery
- Expedited clinical trials
- Reverses gene expression signature of primary liver cancer