Developing an RNA-based Strategy for Actionable Target Assessment to Personalize Cancer Therapies
2020.05.05
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Plan information
Project Term:2019-2020
Budget: About NT$3.3 million

Origin: The Tang Prize is awarded on a biennial basis, each with a cash reward of NT$40 million. Projects proposed by the laureates also receive a grant of up to NT$10 million. The 2018 grant for Biopharmaceutical Science is shared between Dr. Hunter, Dr. Druker, and Dr. Mendelsohn.

 

Project Summary: Background—Although the first wave of precision oncology has focused on genomically informed therapy, many tumors do not have a single strong genomic driver, or have concurrent alterations that may confer resistance. Thus, the “single-gene—single targeted therapy” approach is effective only for a limited number of patients. This suggests that genomic technologies focused on tumor DNA sequencing alone are insufficient and novel approaches to personalizing therapies are needed.

New-generation antibody drug conjugates (ADCs) have shown significant promise. However, ADC trials often screen for one ADC target at a time, leading to inefficiencies in patient identification and delays in patient treatment. Therefore, there is a great need for a multiplex test that can rapidly test for multiple ADC targets—targets that cannot be identified through traditional DNA-sequencing approaches.

 

Since ADCs target proteins on cell surface, it is most appropriate to assess potential targets by their overexpression at the RNA level. Thus, we propose to establish an RNA-based multiplex diagnostic assay to facilitate screening for multiple therapeutic targets and identifying patients with RNA and protein overexpression involving targets of interests (TOIs). These TOIs could be targets of ADCs or potential biomarkers for small molecular inhibitors. After confirming target correlation, analysis will be expanded to additional histologies, including rare tumors.

 

Objectives: our long-term goal is to optimize personalized cancer therapy through the selection of optimal targets identified using more comprehensive methods than DNA sequencing alone. Our short-term goal is to develop a multiplex assay for ADC targets that can be used to identify patients for immunohistochemistry (IHC)-based screening for ADC trials.

 

We will pursue our goals through two specific aims:

 

1.To establish an integrated RNA-based multiplex assay in the pre-CLIA (Clinical Laboratory Improvement Amendments) environment.   

 

2.To compare target expression using our multiplex assay and IHC.

 

Expected outcome: At the end of this project, we expect to have developed a multiplex assay to rapidly screen for ADC targets, enabling us to match patient with ADCs or bio-specific drugs that suit them and to reach our goal of personalizing cancer therapies. Hopefully, this approach will also be adopted in existing or new clinical trials in the future.