The neoplastic cells in the GBC variant of DLBCL, NOS often have mutations in the EZH2, BCL2 and CREBBP genes and overactive PI3K/AKT/mTOR and JAK-STAT signaling pathways while neoplastic cells in the ABC variant often have mutations in the MYD88, CD79A and CD79B (polatuzumab vedotin) genes and overactive B-cell receptor, toll-like receptor, and NF-κB signaling pathways. These different gene mutations and dysregulated signaling pathways are also being studied as potential therapeutic targets for the individualized treatment of GBC and ABC/non-GBC cases. CUDC-907, an inhibitor of PI3K and histone deacetylases, is being evaluated in two separate clinical trials for the treatment of refractory and/or relapsed DLBCL, NOS including cases with alterations in the MYC gene. GSK525762, an inhibitor of the BET family of proteins, suppresses expression of the MYC gene and is undergoing a phase I clinical trial for the treatment of high-grade B-cell lymphoma with MYC, BL2, and/or BL6 rearrangements (i.e. DH/THL). RO6870810, another BET inhibitor, in combination with Venetoclax, an inhibitor of the Bcl-2 protein, is likewise in a phase I clinical trial for the treatment of DH/THL. Pharmacological inhibition of BCL-2 is effective in most B cell lymphomas, but often leads to acquired resistance due to the expression of other major anti-apoptotic BCL-2 family proteins like BCL-XL and MCL-1. Combined therapy using MCL-1 inhibitor (S63845) or BCL-XL inhibitor (A-1331852) in addition to Venetoclax can be a solution to overcome this issue.
It is also contraindicated in newborns and small children, mainly due to the presence of benzyl alcohol, which is included as a preservative. See also
Pentethylcyclanone (similar structure)


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