Double-hit lymphoma (DHL) is a one of the most refractory cancer types. DHLs have several aberrant cancer proteins, including MYC, BCL2 and/or BCL6. Due to simultaneous activation of these cancer-related genes, DHLs do not respond to the current chemotherapy or immunotherapy. Treatment of DHL currently is an unmet medical need. Treatment of DHL is therefore an unmet medical need, which requires a combination of multiple therapeutic approaches.

Targeted therapy contributes to the shrinkage of the tumor burden by directly aiming at cancer cells. However, tumor cells that have lost their response to the drug, will regrow causing a tumor relapse. On the other hand, immunotherapy engages body's ...

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Double-hit lymphoma (DHL) is a one of the most refractory cancer types. DHLs have several aberrant cancer proteins, including MYC, BCL2 and/or BCL6. Due to simultaneous activation of these cancer-related genes, DHLs do not respond to the current chemotherapy or immunotherapy. Treatment of DHL currently is an unmet medical need. Treatment of DHL is therefore an unmet medical need, which requires a combination of multiple therapeutic approaches.

Targeted therapy contributes to the shrinkage of the tumor burden by directly aiming at cancer cells. However, tumor cells that have lost their response to the drug, will regrow causing a tumor relapse. On the other hand, immunotherapy engages body's own immune system to provide long term clinical benefits, which have in some instances resulted in complete cure. Combining targeted and immune therapies may be effective in both reducing the tumor burden and prolonging the survival rate. We have made the observation that by simultaneously inhibiting two cancer proteins, XPO1 and BCL2, we can successfully shrink the size of DHL tumors and prevent their spread.

We propose to examine the therapeutic efficacy of this drug combination using tumor cells from DHL human patients. Furthermore, we plan to add immunotherapy to our current targeted therapy experiments, with the anticipation that the combination of targeted and immune therapeutics will result in long-term survival.

Our study will be performed in close collaboration with an impressive group of experts. If successful, this study may provide a more reliable treatment for one of the most aggressive and unmanageable cancers. Equally important, the proposed studies will lead to a new paradigm for effective cancer treatment that involves simultaneous inhibition of key cancer proteins and activation of the immune system.

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