BGU researchers find promising target for cancer treatment, The researchers have only studied the mechanism in breast cancer models so far, but are currently expanding it to other cancer types as well.
Researchers from the Ben-Gurion University of the Negev have discovered a novel mechanism which is a promising target for cancer therapeutics to optimize cancer treatment, according to a new study published in the peer-reviewed journal Science Advances on Wednesday.
The researchers focused on studying processes in the cell which regulate cancer initiation and progression, specifically gene expression, a multistep process in which genes are transcripted, spliced, translated and eventually lead to a phenotype, an observable trait.
The study found that BRD4, which has a fundamental role in regulation gene expression, inhibits the expression of genes which are involved in translation, in which messenger RNA (MRNA) is translated to a protein, and can abolish protein synthesis, the process through which cells make proteins.
BRD4 methylation, a process that can affect the activity of a DNA segment without changing the sequence, determines the recruitment of the transcription factor E2F1, which regulates DNA transcription on selected target genes which are involved in protein generation, a molecular mechanism which facilitates the balanced expression of these genes. Un-balanced gene expression could lead to increased proliferation and transformation which can then lead to the initiation and progression of cancer.
“Our understanding of human cancer progression and treatment largely depends on our ability to scientifically explore and deeply decipher the different cellular events which control these processes,” said Prof. Dan Levy, a scientist at BGU and the National Institute for Biotechnology in the Negev.
“A central process which regulates cancer pathology is gene expression, or in other words, what are the mechanisms which turns a gene on or off? Can we control a selective gene expression to obtain a delicate balance in cancer-related cellular processes? Can we direct specific cellular factors to regulate this process? Obtaining such a balance will enable the cell to decide which genes to activate in a given time and tissue which will subsequently determine if a cell will become malignant or not,” added Levy.
The researchers have only studied the mechanism in breast cancer models so far, but are currently expanding it to other cancer types as well, such as melanoma and glioblastoma, according to Levy. The lab headed by Levy is studying additional protein methylation pathways, such as cell cycles and programmed cell death.
“These pathways and others have a direct effect on the development of diseases such as different types of cancer and metabolic diseases like diabetes, fatty liver, obesity etc.,” said Levy.
“Our research has great potential for the identification of new therapeutic targets. Indeed, our research group deals with the development of specific molecules to modulate the enzymatic and cellular activity of SETD6 and other methyltransferases. Such agents might be used in the future for the generation of therapy strategies,” added the professor.