Figure 2.

Overview of reported targets in rare lung cancers

(A) A schematic tree model that displays targets covered (left) and not yet covered (right) by FDA-approved biomarkers of each rare lung cancer.

(B) Potential targets and simplified signaling pathways of rare lung cancers. In pLEC, EBV-infected tumor cells can upregulate EBNA1 expression to maintain EBV episome and facilitate oncogenesis. Additionally, TRAF3, a negative regulator of the NF-κB pathway, can be eliminated by the LMP1 protein, which is encoded by EBV, further promoting the NF-κB activity and MHC-I expression. Birinapant can mimic the effect of TRAF3 deficiency and enhance the response to immunotherapy. In pNMC, BET enables the phosphorylation of RNA Pol II to induce oncogene transcription. In PSC, TGFβ could downregulate the transcriptional factor OVOL2 and further activate EMT-drivers (ZEB1 and TWIST) to induce transcription of DDR2 and NCAD. In pACC, the MYB-NFIB fusion may be regulated by AKT-dependent IGF1R signaling.