SciTeMed News Center
The skin cancer which is considered as the most dangerous is melanoma. A vast number of deaths are caused by disease metastasis. Scientists at the Michigan State University have discovered a new drug known as CCG-203971 which is said to have the potential of reducing the melanoma cells from spreading. The spreading of these melanoma cells has been found to be reduced to about 90% in the human body. A journal known as the Molecular Cancer Therapeutics has published these findings.
The compound found in this drug is small-molecular and it controls the ability of the affected genes in producing RNA molecules and proteins which are present in melanoma tumors. The activity of the gene enables the spread of the disease, however, the molecular compound found in this drug is capable of preventing the spread of the disease. The disease scleroderma can be also treated by using the same chemical compound in the drug CCG-203971.
So far, only few existing compounds have been found to be capable of preventing the spread of the melanoma cells. Prof. Richard Neubig who works at the Department of Pharmacology and Toxicology at the Michigan State University says that till now, it has been a challenging feat to block the activity of gene which acts as a mechanism for signaling the melanoma progression by developing small-molecular drugs. CCG-203971 works wonders in preventing the spreading of melanoma cells in the human body.
It was discovered by Neubig et al. that the proteins known as myocardin-related transcription factors (MRTFs) can be stopped by this compound from starting the gene transcription process in the melanoma cells. Another protein called as the Ras homology C (RhoC) triggers the MRTFs. The RhoC protein is found in the signaling pathway which causes the aggressive spread of the disease in the body. There exists evidence of Rho-activated gene transcription in the metastasis of melanoma which is mediated by the nuclear localization of MRTFs. MRTF acts as the transcriptional co-activator. The role for Rho and MRTF signaling and its reversal can be evidenced by pharmacologic inhibition making use of in vitro and in vivo models of human melanoma growth and metastasis.
This drug CCG-203971 enables the reduction in the migration of the melanoma cells. The reduction takes place at 85 to 90%. This drug also has the potential of reducing tumors in the lungs of mice which were first injected with the melanoma cells of humans. Prof. Neubig says that they screened the chemical inhibitors by making use of melanoma cells which were intact. This enabled them to discover the compound that could block RhoC pathway anywhere. With the blocking of this entire pathway, they were able to detect the MRTF signaling protein as the new target.
Kate Appleton who is the co-author and a postdoctoral student in the Department of Pharmacology and Toxicology at Michigan State University says that they figured out that the next step in the development of the compound is in finding out which patients had this pathway turned on. This enabled them to detect which patients would benefit the most in the use of this compound.
It is said that when this pathway is activated, the effect of the drug CCG-203971 is much stronger in enabling the shutting down of the cell growth of the melanoma and its progression in the human body. The activation of the MRTF proteins in the human body is considered as a biomarker in the determination of risk and other factors, especially for all those human beings who are affected by melanoma in the early stages.
The study links Rho and MRTF-mediated signaling with aggressive phenotypes. The results support targeting the MRTF transcriptional pathway as a novel approach to melanoma therapeutics.
Andrew J. Haak et al. 2017. Pharmacological Inhibition of Myocardin-related Transcription Factor Pathway Blocks Lung Metastases of RhoC-Overexpressing Melanoma. Mol Cancer Ther 16 (1): 193-204; doi: 10.1158/1535-7163.