Chinese scholar Molecular Cell published a paper, revealing the molecular typing of KRAS mutant tumors and new strategies for precise treatment

On August 9, 2021, the team of Researcher Tan Minjia and Researcher Huang Min from the Shanghai Institute of Materia Medica, Chinese Academy of Sciences published online research results titled "A proteomic and phosphoproteomic landscape of KRAS mutant cancers identify combination therapies" in Molecular Cell
.

This study reveals new molecular typing and precision treatment strategies for KRAS mutant tumors

KRAS is one of the oncogenes with the highest mutation rate in human malignant tumors, accounting for about 15% to 20% of all tumor patients.
It is an important cancer driver gene for lung cancer, colorectal cancer, pancreatic cancer and other tumors with high mortality
.

The treatment of KRAS mutant tumors has always attracted much attention in the field of tumor research.

KRAS mutation promotes tumorigenesis and development by continuously activating a large number of phosphorylation signal transduction pathways in cells
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In the context of KRAS mutations, a panoramic picture of tumor proteome and phosphorylation modification signaling pathways is expected to bring breakthroughs in the molecular typing of KRAS mutations and guide the discovery of new strategies for precise treatment

Based on the above research strategy, this study conducted a systematic analysis of proteomics and phosphorylation modification omics on 43 KRAS mutant tumor cells from different tissue sources
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Through the integration of genome-proteome-phosphoproteomics data, KRAS mutant cells were divided into three subtypes with different biological characteristics, and the molecular typing of large-scale clinical tumor samples was further realized, which confirmed the molecular classification.

On the basis of precise classification, this research continues to explore in depth the potential therapeutic targets, therapeutic drugs and pharmacodynamic biomarkers of KRAS mutant tumors
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More meaningfully, through the integrated analysis of protein phosphorylation and susceptibility data, this work proposed for the first time a combination drug prediction method based on the "signaling pathway complementary strategy", and found a series of potential synergistic anti-tumor effects.

This research breaks through the limitations of the current molecular typing research that mainly relies on the genome, reveals the molecular characteristics of the KRAS mutant tumors at the proteome and phosphorylation levels, and discovers a new subtype-specific precision treatment strategy, which is an in-depth understanding of KRAS.
The heterogeneity of mutant tumors and the realization of precise treatment have proposed innovative ideas
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　　The first authors of this research paper are the PhD students Liu Zhiwei and Liu Yingluo of the Shanghai Institute of Materia Medica.
Researcher Tan Minjia and Researcher Huang Min are the co-corresponding authors of this paper
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The research was guided and helped by Academician He Fuchu of the National Center for Protein Science of the Academy of Military Sciences and Professor Li Jing of Shanghai Jiaotong University

　　Original link: https://doi.

New strategies for molecular typing and precision treatment of KRAS mutant tumors based on multi-omics

　　(Contribution department: Tan Minjia research group)