ICC 2022

Alexander Plotnikov

Alexander Plotnikov, Speaker at Cancer Congress 2022
Weizmann Institute of Science, Israel
Title : Differentiations of colon cancer induced by inhibition of PRMT1

Abstract:

Colorectal cancer (CRC) is the third most commonly occurring cancer in men and the second most commonly occurring cancer in women. CRC incidence and number of deaths are rapidly growing over the World. Number of new cases jumped from 800,000 to 2,000,000 in the last 30 years. Prognosis for the year 2040 is about 3,200,000 new cases.

Despite the development of cancer therapy, number of deaths raised from 500,000 in the year 1990 to about 1,000,000 in the year 2021. Differentiation therapy has been recently revisited as a prospective approach in cancer therapy by targeting the aberrant growth, and repairing the differentiation and cell death programs of cancer cells. Standard of care chemotherapy may kill cancer cells, but aggressive cells can survive and resistance gradually develops. In contrast, differentiation therapy aims not to eradicate cancer bulk, but rather directs cancer cells towards inhibited proliferation and restoration of the apoptotic program, while maintaining a limited toxicity. However, differentiation therapy of solid tumors is a challenging issue and progress in this field is limited. We performed High Throughput Screening (HTS) of about 6000 compounds using a novel dual multiplex assay in order to discover compounds, which induce differentiation of human colon cancer cells (HT-29). We found that protein arginine methyl transferase (PRMT) type 1 inhibitor, MS023, is a potent inducer of colon cancer cell differentiation with a large therapeutic window. Differentiation changes in the aggressive human colon cancer cells were proved by proteomic and genomic approaches. Growth of HT-29 xenograft in nude mice was significantly delayed upon MS023 treatment and immunohistochemistry of tumor indicated differentiation changes. These findings might lead to development of clinically effective anti-cancer drugs based on the mechanism of cancer cell differentiation.

 

Biography:

Dr. Alexander Plotnikov studied Human Biology at the Tel-Aviv University, in the research group of Prof. Yona Keisari and received his PhD degree in 2005. He did 2 postdoctoral fellowships, first in the Penn University, USA in the group of Prof. Serge Fuchs, and second in Weizmann Institute of Science (WIS) in the lab of Prof. Rony Seger. His specialization is cancer biology. In 2012, Wohl Drug Discovery Institute has been established in WIS, and Alexander is one of the pioneers in that facility. He was a Project Leader in about 100 scientific projects, co-author of 27 research articles.

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