Advancements in proteogenomics for preclinical targeted cancer therapy research repair
image: Proteogenomics and their applications in target cancer therapy research. The application of proteogenomics (mainly including genomics, transcriptomics, and proteomics) has become an indispensable tool in the diagnosis and treatment of various types of cancer. Through the assessment of alterations, molecular expressions, cell populations, sample subtyping, and other aspects, proteogenomics can provide invaluable insights into preclinical target cancer therapy research. This includes unraveling the mechanism of tumorigenesis, identifying potential targets and specific biomarkers, and predicting subtype-specific therapy
Credit: Yuying Suo, Yuanli Song, Yuqiu Wang, Qian Liu, Henry Rodriguez, Hu Zhou
Key Findings:
- Comprehensive Molecular Insights:
Proteogenomics integrates genomics, transcriptomics, and proteomics to provide a multidimensional understanding of tumor biology, uncovering functional consequences of genetic alterations that are not evident at the DNA or RNA level alone. - Discovery of Novel Therapeutic Targets:
By analyzing post-translational modifications (PTMs) and protein expression patterns, proteogenomics has enabled the identification of previously unrecognized druggable targets, particularly in tumors with limited actionable mutations. - Refinement of Cancer Subtypes:
Multi-omic profiling facilitates the reclassification of tumors into biologically and clinically relevant subtypes, offering insights into subtype-specific vulnerabilities and guiding precision treatment strategies. - Immune Landscape Characterization:
Proteogenomic approaches enhance the resolution of tumor microenvironment components, including immune cell infiltration and immune checkpoint expression, which are critical for immunotherapy development and response prediction. - Integration of Single-Cell and Pan-Cancer Analyses:
Emerging single-cell proteogenomic techniques reveal intratumoral heterogeneity and rare cell populations, while pan-cancer studies highlight conserved and distinct molecular mechanisms across tumor types, informing broader therapeutic strategies.
Significance:
Proteogenomics represents a paradigm shift in preclinical cancer research by bridging the gap between genomic alterations and functional protein biology. This integrative approach enables a more accurate interpretation of how mutations translate into biological behavior, facilitating the discovery of novel therapeutic targets, predictive biomarkers, and rational combinations for targeted and immune therapies. Its application in subtype-specific and pan-cancer studies holds the potential to transform clinical decision-making and accelerate the development of next-generation precision oncology strategies.
The work entitled “Advancements in Proteogenomics for Preclinical Targeted Cancer Therapy Research”was published on Biophysics Reports (published on Feb. 2025).