[ExI] Reprogramming cancer cells

[Stuart LaForge]

On 2024-12-28 21:04, Stuart LaForge wrote:
> These researchers at the bioengineering departments at the Korea 
> Advanced Institute of Science and Technology used computational biology 
> techniques to develop a Boolean model of gene regulatory networks in 
> cells they call BENEIN. They then used it on human large intestinal 
> single-cell transcriptome data to identify three genes MYB, HDAC2, and 
> FOXA2 as "master regulatory genes" for differentiation into normal 
> intestinal cells. Then they claim that they took three different colon 
> cancer cell lines and by knocking down, i.e. shutting off those three 
> genes, made the cancer cells back phenotypically normal large intestine 
> cells.
> 
> https://onlinelibrary.wiley.com/doi/10.1002/advs.202402132
> 
> ---------Excerpt------------------
> 
> Control of Cellular Differentiation Trajectories for Cancer Reversion
> Jeong-Ryeol Gong, Chun-Kyung Lee, Hoon-Min Kim, Juhee Kim, Jaeog Jeon, 
> Sunmin Park,and Kwang-Hyun Cho*
> 
> Abstract:
> Cellular differentiation is controlled by intricate layers of gene 
> regulation, involving the modulation of gene expression by various 
> transcriptional regulators. Due to the complexity of gene regulation, 
> identifying master regulators across the differentiation trajectory has 
> been a longstanding challenge. To tackle this problem, a computational 
> framework, single-cell Boolean network inference and control (BENEIN), 
> is presented. Applying BENEIN to human large intestinal single-cell 
> transcriptome data, MYB,HDAC2, and FOXA2 are identified as the master 
> regulators whose inhibition induces enterocyte differentiation. It is 
> found that simultaneous knockdown of these master regulators can revert 
> colorectal cancer cells into normal-like enterocytes by synergistically 
> inducing differentiation and suppressing malignancy, which is validated 
> by in vitro and in vivo experiments.
> 
> --------------------------------------
> 
> Note that that they use "in vivo" in a biochemical sense which means 
> inside a living cell and not medical "in vivo" which means inside an 
> intact organism like a mouse or human.
> 
> Stuart LaForge

Well ok. They did use grafts of the cell lines into nude mice, but that 
is barely in vivo and is very different than reversing colon cancer in a 
mouse.

Stuart LaForge