Project title: Exploring new therapeutic avenues for SDHB-deficient metastatic PPGL

Description

What critical problem/question will researchers try to answer?
Our study will address a critical neuroendocrine cancer question of identifying and understanding the vulnerabilities of SDHB-deficient pheochromocytoma and paraganglioma (PPGL), rare tumors that develop in the adrenal medulla and extra-adrenal paraganglia.

Why is this important?
Although surgery can often cure PPGLs, some tumors recur or spread to other parts of the body prior to surgical removal. Unfortunately, when PPGLs become metastatic, to places like the lymph nodes, bones, lungs, or liver, treatment options are ineffective – less than 60% of patients with metastatic PPGL survive for 5 years beyond the time of diagnosis. PPGLs with an SDHB mutation have a significantly increased metastatic risk, with about 30% of these tumors becoming metastatic. The major barrier to treating metastatic PPGLs is the lack of effective therapies. Understanding the specific vulnerabilities of PPGLs with SDHB mutations is a critical step toward developing more targeted and effective treatments.

What will the researchers do?
We will employ a combination of high-throughput drug and genetic (CRISPR/Cas9) screening to identify vulnerabilities specific to SDHB-deficient PPGLs.

How might this improve treatment of NETs?
Our work addresses the urgent need to reshape the clinical approach to treating patients with metastatic SDHB-deficient PPGLs, offering the possibility of a personalized, precision-medicine approach to treating a challenging neuroendocrine disease with poor prognosis and limited treatment options.

What is the next step?
Our next step is to understand the mechanism of action of newly identified SDHB-selective medications and develop improved treatments that leverage newly identified therapeutic targets.

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