PCDHB15 (Protocadherin Beta 15)

We explored the role of PCDHB15 in melanoma aggressiveness and showed that overexpression impairs invasiveness and aggregation of metastatic melanoma cells in vitro and formation of lung metastasis in vivo. These findings highlight important modifications of the methylation of the PCDHβ genes in melanoma and support a functional role of PCDHB15 silencing in melanoma aggressiveness.

Taken together, PCDHB15 is a potential tumor suppressor in cases of breast cancer, which can be epigenetically silenced via promoter methylation. PCDHB15 methylation using cfDNA is a novel minimally invasive epigenetic biomarker for the diagnosis and prognosis of breast cancer.

The most effective treatment option to date is alemtuzumab, an anti-CD52 monoclonal antibody...The tested drugs were idasanutlin (MDM2 inhibitor), cladribine (purine analog), venetoclax (Bcl-2 inhibitor), ruxolitinib (JAK inhibitor), romidepsin (histone deacetylase inhibitor), dinaciclib (CDK inhibitor), ibrutinib (BTK inhibitor) and bendamustine (alkylating agent)...Idasanutlin in combination with cladribine resulted in the most synergistic combination, but only in selected patients (8/20). Conclusion Transcriptomic changes together with gender may explain variable responses to targeted treatments in T-PLL cells ex vivo, suggesting personalized treatment options.

In CRC cells that express activated KRAS, SLC25A22 promotes accumulation of succinate, resulting in increased DNA methylation, activation of WNT signaling to β-catenin, increased expression of LGR5, proliferation, stem cell features, and resistance to 5-fluorouacil. Strategies to disrupt this pathway might be developed for treatment of CRC.