Patent for Bozepinib approved by scientists of University of Granada
Researchers at the University of Granada, Spain, have patented Bozepinib, a drug that inhibits the growth of cancer stem cells in breast, colon and melanoma cancers.
The mechanisms of action of Bozepinib were first described in an article published in the Open Access journal Oncotarget back in 2014. The team showed that Bozepinib was able to inhibit growth and metastasis of tumors in mice without inducing toxicity. Follow-up studies have proved that the drug was able to reduce tumor activity by 50% after forty-one days of treatment.
Bozepinib’s powerful anti-tumorigenic properties are mainly due to the inhibition of HER-2 signaling pathways. In normal cells HER-2 protein is associated with survival, growth and proliferation. However, HER-2 is over-expressed in cancer cells, ultimately leading to a poor prognosis and decreased overall patient survival rate. This makes HER-2 one exciting target for anti-cancer therapies. The ability to target cancer stem cells is one of the aspects that makes Bozepinib a promising drug in cancer treatment.
Cancer stem cells
Several studies suggest that stem cells are one of the cell subsets present within the bulk of a tumor. Stem cells have unique properties: they maintain the ability to renew themselves and give rise to cells specific for each tissue of the body. Like normal adult stem cells, cancer stem cells can divide indefinitely and give rise to to a variety of cancer cell types, including more cancer stem cells. Moreover, cancer stem cells are able to detach themselves from the bulk of the tumor, enter the bloodstream and invade other tissues, therefore contributing to the process of metastasis.
The model of cancer stem cells contrasts to the stochastic model, which argues that tumors are biologically homogenous and all cancer cells have the same potential to grow and divide, but each cell chooses at random between self-renewal and differentiation.
The first evidence to support the existence of cancer stem cells came from studies into leukemia, where it was clear that only a small fraction of leukemia cells transplanted to a healthy donor could give rise to leukemia. Since then, several reports have shown the existence of this specific subset of cells in solid tumors. Nevertheless, the existence of cancer stem cells still remains controversial. One of the main points of contention that faces criticisms is the technical difficulty involved in the isolation of cancer stem cells in the tumor. Critics of the cancer stem cell model argue that, so far, the studies that prove their existence are not able to mimic the natural microenvironment in which these cells act on the tumor.
The existence of cancer stem cells has major implications for the way cancer gets treated. Cancer therapies aim to kill fast dividing cells in the bulk of the tumor but spare the slow dividing cancer stem cells. These surviving cells are then able to drive the regrowth of the tumor. Hence, targeting the cancer stem cells might offer a significant improvement in the cancer therapies.
What does the future hold?
The patent of Bozepinib was the result of 22 years of research. The next steps towards clinical trials involve detailed studies of toxicity and safety, as well as the study of the metabolic implications the drug might have on the organism. The group will also proceed to study the impact of the drug in other cancer types, specifically lung and pancreas cancers, two of the most aggressive types of cancers.
Meanwhile, as the crucial role of cancer stem cells is becoming clearer, it is important to redirect the focus of cancer research and open the market for new cancer stem cell therapies. This will certainly contribute to a better understanding of how cancer works and, eventually, brighter prospects for cancer patients.
Ramírez A, Boulaiz H, Morata-Tarifa C, Perán M, Jiménez G, Picon-Ruiz M, Agil A, Cruz-López O, Conejo-García A, Campos JM, Sánchez A, García MA, & Marchal JA (2014). HER2-signaling pathway, JNK and ERKs kinases, and cancer stem-like cells are targets of Bozepinib small compound. Oncotarget, 5 (11), 3590-606 PMID: 24946763
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