Paper - Review

DOI: 10.1016/j.cell.2021.07.016

In brief

Comprehensive proteogenomic characterization
← of 1⃣ lung squamous cell carcinomas 2⃣ paired normal adjacent tissues
→ identifies
→ 1⃣ taxonomic sub-classes 2⃣ alternative driver events 3⃣ insight → into immune modulation
∴ 1⃣ putative biomarkers 2⃣ potential therapeutic targets

Highlights

Unsupervised clustering
→ revealed subtype
← with 1⃣ EMT 2⃣ phosphoprotein signatures

Potential therapeutic vulnerabilities
← included 1⃣ survivin 2⃣ NSD3 3⃣ LSD1 4⃣ EZH2

Rb phosphorylation
→ nominated ← as a biomarkers
→ for trials with CDK4/6 inhibitors

Detailed immune landscape analysis
→ highlighted → targetable points ← of immuneregulations

Summary

Lung squamous cell carcinoma (LSCC)
→ remains → a leading cause of cancer death
← with few therapeutic options

Characterized → the proteogenomic landscape of LSCC
→ providing a deeper exposition of LSCC biology
← with potential therapeutic implications

Identify NSD3
← as 1⃣ an alternative driver ← in FGFR1-amplified tumors
← as 2⃣ low-p63 tumors over-expressing the therapeutic target survivin

SOX2
→ is considered undruggable
Our analyses
→ provide rationale
→ for exploring chromatin modifiers ← e.g. 1⃣ LSD1 2⃣ EZH2
→ to target SOX2-over-expressing tumors

Our data
→ support complex regulation ← of metabolic pathways
← by crosstalk ← between post-translational modifications ← e.g. ubiquitylation

Numerous immune-related proteogenomic observations
→ suggest → directions → for further investigations

Proteogenomic dissection of CDKN2A mutations
→ argue → for more nuanced assessment ← of 1⃣ RB1 protein expression 2⃣ phosphorylation
← before declaring CDK4/6 inhibition unsuccessful

Triangulation
← between 1⃣ LSCC 2⃣ LUAD 3⃣ HNSCC
→ identified → both (unique & common) therapeutic vulnerabilities

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