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Published on: September 19, 2018
The Evolution of Oncology Companion Diagnostics from Signal Transduction to Immuno-Oncology
Nicholas C Dracopoli1, Mark S Boguski2
1Janssen Research & Development, 1400 McKean Road, Spring House, PA 19477, USA.
Abstract:
Sixteen oncology drugs have been approved with a companion diagnostic (CDx) test by the FDA. These represent only 9.6% of the 167 oncology drug approvals since 1998, the year the first CDx test for Herceptin was approved. The great majority of CDx tests are for drugs that inhibit signal transduction pathways by either inhibiting the intracellular kinase activity with a small molecule or preventing ligand-induced receptor activation with a monoclonal antibody. In most of these cases, prospective patient selection for the biomarker-positive subpopulation was initiated in or before Phase II. The development of CDx tests for emerging immunotherapies will be more complicated because they are not dependent on driver mutations in the drug target, the mechanism of action is often pleiotropic, and will require both protein and cell-based assays to evaluate the interaction of the tumor with the immune system. Consequently, we will need to develop new biomarker strategies for the development of immunotherapies and to determine whether the optimum strategy is to release a prior checkpoint blockade in patients with a suppressed immune response, or to prime a new immune response to the tumor.
Insights
Companion diagnostic (CDx) tests are crucial for oncology drug approvals, but most target signal transduction pathways. Developing CDx tests for immunotherapies presents new challenges requiring novel biomarker strategies.
Area of Science:
- Oncology
- Biomarkers
- Drug Development
Background:
- Only 9.6% of 167 oncology drugs approved since 1998 have companion diagnostics (CDx).
- Most existing CDx tests are for signal transduction inhibitors, utilizing prospective patient selection early in clinical trials.
- The first CDx test was approved in 1998 for Herceptin.
Purpose of the Study:
- To analyze the landscape of FDA-approved oncology drugs with companion diagnostics.
- To highlight the complexities in developing CDx tests for emerging immunotherapies.
- To propose the need for new biomarker strategies for immunotherapy development.
Main Methods:
- Review of FDA oncology drug and companion diagnostic approvals since 1998.
- Analysis of the types of drugs and targets associated with companion diagnostics.
- Discussion of the challenges and potential strategies for immunotherapy CDx development.
Main Results:
- Sixteen oncology drugs have approved companion diagnostics, representing 9.6% of total approvals.
- The majority of CDx tests are for small molecule kinase inhibitors or monoclonal antibodies targeting signal transduction pathways.
- Immunotherapies present unique challenges due to non-driver mutation targets and pleiotropic mechanisms.
Conclusions:
- Developing companion diagnostics for immunotherapies requires new biomarker strategies.
- Assays must evaluate the complex tumor-immune system interaction for immunotherapies.
- Future strategies may involve checkpoint blockade or priming immune responses.
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