Despite the tremendous efforts devoted to fighting cancer for the last half century, cancer is still the leading cause of death worldwide. Many chemo, radiational and targeted therapeutic approaches have improved the lifespan of cancer patients to a certain extent. However, many intrinsic or developed resistances to such treatments have created obstacles in freeing humanity from the disease. 

In long term research, we found that an epigenetic modulator is related to the radio-resistance of lung cancers. Through a proteomic approach, we identified the chromatic remodeling factors, which are known to repair the double-strand DNA breakage, are regulated by this modulator. Currently we are investigating the detailed mechanism of how the modulator regulates the DNA repair and how to apply this to the therapy.

It has been shown that some targeted therapeutics may kill the cancer cells more selectively in synthetics lethal settings.  The PARP inhibitors significantly improved recurrence free survival of the BRCA mutant ovarian and breast cancer patients.  

With a crispr-dCAS9 screening using 200,000 guide RNAs targeting transcription regulation of 20,000 genes on 2 TNBC cell lines, we identified several novel candidate genes for the synthetic lethal targeting with PARP inhibitors on TNBC. Preliminary results showed some of those are novel repair molecules like BRCA1 and can be used for the biomarker of PARPi inhibitor susceptibility. We also found that  some immune signaling axis contribute the PARPi efficacy and are pursuing the molecular mechanism study further.