June 20, 2013, New York, NY and Oxford, UK An advanced tumor is a complex ecosystem. Though derived from a single cell, it evolves as it grows until it contains several subspecies of cells that vary dramatically in their genetic traits and behaviors. This cellular heterogeneity is what makes advanced tumors so difficult to treat. Publishing their findings in today's online issue of Cancer Cell, an international team of scientists led jointly by Professors Colin Goding from the Ludwig Institute for Cancer Research who is based at the University of Oxford and Jos Neptuno Rodriguez-Lpez from the University of Murcia, Spain describe a therapeutic strategy that manipulates a mechanism driving that heterogeneity to treat advanced melanoma. Their preclinical studies show that the strategy, which employs a new drug-like molecule in combination with an existing chemotherapy, is highly specific to melanoma cells and effective against tumors that resist all other therapies.
If caught early, melanoma is relatively easy to treat. But in its late stages, it is a stubborn and deadly cancer. Until about a decade ago, patients survived only about seven months after starting treatment. Since then, therapies, such as vemurafenib, that specifically target signaling proteins essential to the proliferation and survival of melanoma cells have extended the lives of some patients. But only about half respond to these targeted therapies, and even in those patients the cancer begins to resist the targeted therapy within six to nine months.
To bypass such resistance, the researchers developed a strategy that essentially pushes subtypes of melanoma cells that are not dividingand are therefore not susceptible to chemotherapyto become vulnerable to a shrewdly targeted drug.
To develop their therapy, the scientists first screened a variety of molecules to find one that boosts the expression of MITF, a master gene that, at high levels, pushes melanoma cell
|Contact: Rachel Steinhardt|
Ludwig Institute for Cancer Research