Liver cancer – a major global problem requiring new treatments
Liver cancer is increasing in incidence, faster than any other cancer, and presents a major global challenge. Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver accounting for ~700,000 deaths worldwide annually, and the incidence is increasing. The prognosis for patients with HCC remains poor (<10% 5-year survival rate).
Although traditional risk factors for HCC have included hepatitis infections and alcohol, the most important risk factors now are obesity and type 2 diabetes. These disorders lead to an inflammation in the liver called NASH, which predisposes to HCC. Given that ~1/3 of the world is either overweight or obese and ~10% have type 2 diabetes, its no wonder that liver disorders of fat metabolism and HCC are becoming such an important area of clinical need.
There is only one drug currently available for advanced HCC, Sorafenib. Its clinical effects are modest and everyone develops resistance and a precipitous downhill course and death. Given the paucity of effective treatments and its poor prognosis HCC represents huge unmet clinical need and new drugs are urgently needed, as well as better ways to prevent the disease, hopefully intervening in the NASH stage and blocking its progression to cancer.
miR-7 and development of mRx-7 to treat liver cancer
mRx-7 is being developed to treat recalcitrant cancers for which the prognosis is poor and there are few, if any, treatments. These include HCC, head and neck cancer and advanced melanoma. We envisage mRx-7 would be used in conjunction with other small molecule inhibitors, such as sorafenib, as well as with chemotherapy agents, and potentially with other forms of immunotherapy.
mRx-7 is a chemical mimic of miR-7 with second generation chemistry modifications designed to stabilize it in the body and to enhance delivery directly to the liver. It is a potent inhibitor of EGFR and its downstream signalling pathways and HCC growth.
It is synergistic with Sorafenib in HCC and can restore sensitivity to the drug in resistant cells, which is a major advantage of mRx-7 over other HCC therapies.
mRx-7 has been designed to go into early phase clinical trials in patients with HCC, either alone or in combination with sorafenib or other therapies, such as immunotherapy.