ArticleMolecular oncology2024
A novel pipeline for prioritizing cancer type-specific therapeutic vulnerabilities using DepMap identifies PAK2 as a target in head and neck squamous cell carcinomas.
Article in Molecular oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 11 citations in OpenAlex.
- Multimodal analysis reveals potential association of CDH13 with endothelial cells and its overexpression in hepatocellular carcinoma.European journal of medical research · 2025Article
- Integrating large-scale in vitro functional genomic screen and multi-omics data to identify novel breast cancer targets.Breast cancer research and treatment · 2025Article
- The overexpression of HOXC6 in LUSC and pan-squamous cell carcinomas indicates the coexistence of nuclear division regulatory mechanisms.Cancer biomarkers : section A of Disease markers · 2025Article
- Identification and characterization of survival-dependent genes in esophageal cancer via the DepMap database: unraveling their association with immune infiltration.Discover oncology · 2025Article
- New insights into the role of mitophagy related gene affecting the metastasis of osteosarcoma through scRNA-seq and CRISPR-Cas9 genome editing.Cell communication and signaling : CCS · 2024Article
- Tumor suppressor ACER1 correlates with prognosis and Immune Infiltration in head and neck squamous cell carcinoma.Scientific reports · 2024Article
- Genome wide-scale CRISPR-Cas9 knockout screens identify a fitness score for optimized risk stratification in colorectal cancer.Journal of translational medicine · 2024Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
There is limited guidance on exploiting the genome-wide loss-of-function CRISPR screens in cancer Dependency Map (DepMap) to identify new targets for individual cancer types. This study integrated multiple tools to filter these data in order to seek new therapeutic targets specific to head and neck squamous cell carcinoma (HNSCC). The resulting pipeline prioritized 143 targetable dependencies that represented both well-studied targets and emerging target classes like mitochondrial carriers and RNA-binding proteins. In total, 14 targets had clinical inhibitors used for other cancers or nonmalignant diseases that hold near-term potential to repurpose for HNSCC therapy. Comparing inhibitor response data that were publicly available for 13 prioritized targets between the cell lines with high vs. low dependency on each target uncovered novel therapeutic potential for the PAK2 serine/threonine kinase. PAK2 gene dependency was found to be associated with wild-type p53, low PAK2 mRNA, and diploid status of the 3q amplicon containing PAK2. These findings establish a generalizable pipeline to prioritize clinically relevant targets for individual cancer types using DepMap. Its application to HNSCC highlights novel relevance for PAK2 inhibition and identifies biomarkers of PAK2 inhibitor response.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.