Diagnostic Assay for Determining Patient Response to Apoptosis-related Cancer Therapy

Many known chemotherapeutic drugs kill abnormal cells through a process called apoptosis. Bcl-2 proteins are negative regulators of apoptosis that control cell survival and death. Increased expression of anti-apoptotic Bcl-2 proteins commonly occurs in up to 30% of all cancers, providing cancer cells a pro-survival advantage to evade cell death, grow, and proliferate. Drugs targeting these specific anti-apoptotic proteins are potential anti-cancer therapeutics. A need exists for improved methods to select patients that may benefit from drugs targeting apoptotic pathway, such as Bcl-2 homology domain-3 (BH3) mimetics. 

Researchers at the NCI developed a multiplex assay to determine the efficacy of apoptosis-related drugs targeting the Bcl2 family of proteins or aid in the selection of cancer patients likely to respond. The immunoassay quantitatively measures heterodimer protein complexes of specific Bcl-2 family proteins. Traditional assays performed in needle biopsies only measure individual Bcl-2 family proteins and do not capture the protein-protein interactions.   

The assay was confirmed using tumor tissue biopsy samples and has the potential to predict drug efficacy. The assay may be useful as a companion diagnostic in conjunction with apoptosis-inducing agents.  The assay also has the potential to aid in the selection of cancer patients likely to respond to drugs targeting the apoptosis pathway.  

Potential Commercial Applications: Competitive Advantages:
  • Companion diagnostic to determine efficacy of anti-apoptotic therapies such as BH3 mimetics 
  • Diagnostic for the selection of appropriate drug therapy for cancer patients 
  • Novel assay to simultaneously measure multiple indicators of apoptosis in a single sample compared to traditional assays
  • Quantitative measurement of pro-apoptotic drug efficacy

Development Stage:


Apurva Srivastava

Dominic Esposito

Jeevan Govindharaju

Ralph Parchment

James Doroshaw (NCI)  ➽ more inventions...

Intellectual Property:
Application No. 62/798,615
Application No. US 2020/015694

Srivastava AK, et al. Effect of a Smac Mimetic (TL32711, Birinapant) on the Apoptotic Program and Apoptosis Biomarkers Examined with Validated Multiplex Immunoassays Fit for Clinical Use.  PMID 26446940

Collaboration Opportunity:

Licensing only

Licensing Contact:
John Hewes, Ph.D.
Email: John.Hewes@nih.gov
Phone: 240-276-5515

OTT Reference No: E-195-2018
Updated: Apr 1, 2020