New York University and USC have collaborated to create a breakthrough project in cancer treatment. Together, they have developed a new synthetic molecule that will disrupt the “conversation” between cancer cells in the human body.
According to a press release, the synthetic molecule created targets the interaction between two proteins, causing the genes to promote tumor progression. This compound was specifically designed to interrupt the type of molecular conversation within the cell that promotes the growth of cancer cells and tumor progression. The NYU team is lead by chemistry professor Paramajit Arora, and the USC team is led by the USC School of Pharmacy professor Dr. Bogdan Olenyuk.
“Professor Paramjit Arora and I studied together at Caltech,” Olenyuk said. “He is an expert in bioorganic chemistry and chemical biology, specifically in the design of synthetic protein mimetics, and we have been working on this project since 2007.”
HBS1, the synthetic molecule described in their paper, limits tumor progression. The method required for locking the correct spiral helical shapes in synthetic strings of amino acids was developed at NYU.
“Our designed compound selectively disrupts expression of genes required for tumor progression and metastasis,” Olenyuk said.
The results from this research project could be tremendously important for the future in the scientific community.
“These results could dramatically improve several types of cancer therapies currently used in the clinic,” Olenyuk said.
Dr. Ramin Dubey, a member of Olenyuk’s team, who worked toward the development of small molecule therapeutics that targets angiogenesis, or formation of new blood vessels in tumors, was involved in development of two classes of molecules.
“Our approach works on transcriptional level of cancer progression by inhibiting the transcription factor HIF-1,” Dubey said. “Inhibiting the transcription factors directly is, in theory, a very powerful approach but not many practical examples are known for this strategy. Our work is a significant step in showing the practical relevance of this approach.”
Dr. Swati Kushal, a USC School of Pharmacology postdoctoral scholar, also contributed to the project by exploring the biological potential of the rationally designed compounds that can selectively disrupt the a transcription factor complex and hence down-regulate the expression of genes critical for tumor progression and metastasis.
“Our research has demonstrated the potential of designed protein secondary structure mimetics to become new research tools for disruption of protein-protein interfaces involved in transcription factor complex,” Kushal said.
The work will likely revolutionize the cancer treatment drug creation process.
“Of all the proteins in cells, less than 20 percent are considered as druggable,” Kushal said. “With the innovative approaches in hand, I would hope that it would be possible to raise this bar that would ultimately lead to the discovery of novel therapeutics.”
USC researcher Hanah Mesallati was involved in maintaining the cancer cell lines and carrying out in vitro cell-based assays, including viability and luciferase studies.
“The results of this research show that transcription factor protein domain mimetics can halt the growth of tumors in vivo,” Mesallati said. “Hopefully this research will eventually lead to the development of pharmaceutical agents, which will form part of an effective multi-drug chemotherapy regime.”
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