This blog is based on a published review by Weber et al. International Journal of Molecular Sciences.
Patient stratification in clinical trial design.
Traditional non-targeted cytotoxic drugs in cancer treatment often lack specificity. This leads to toxicity in healthy tissues such as gut and bone marrow. With targeted therapy you can prevent these unwanted side effects. This approach uses anticancer agents that selectively address specific molecular markers on cancer cells.
However, the expression of a molecular target is usually not present on tumors in all patients. This means that targeted anticancer agents tend to not work in all patients. Therefore, when designing your clinical trial, you must select patients that express your target. This process is also referred to as patient stratification. If you don’t include patients that express your target you run the risk of a negative trial outcome that is based on the lack of the presence of the target and not on the lack of the efficacy of the drug. Clearly, targeted anti-cancer treatment, by definition, is not a tale of ‘one-size-fits-all’.
How to determine tumor characteristics.
First, it is important that you gather data on tumor characteristics to exploit the potential of your drugs in the drug development process. There are three main approaches you can use to examine target expression:
- Gene expression analysis and cancer proteomics
- Immunohistochemistry of biopsies and/or the resected specimen
- Molecular imaging
The first two approaches required biopsies. However, biopsies don’t give you information on target expression of complete organs, let alone whole-body information. By using molecular imaging, option 3, you do get whole-body information on target expression on an organ level. This is important because organs or tissues can have heterogenous expression of the target. With biopsies you cannot show this heterogenous expression, but with molecular imaging you can.
Molecular imaging for patient and cancer stratification.
You can use molecular imaging for cancer stratification and localization (i.e. cancer staging). Cancer staging is critical in clinical decision-making for either palliative or curative intend of a treatment scheme. Foremost, it gives you the unique ability to predict the possible effect and outcome for the individual patient. An individual blueprint for the patient. Namely, by imaging you get information whether the patient’s tumor, and possible metastases, can be treated by the targeted cancer treatment. After all, why treat the cancer for a target expression when the target is not present?
Read more about this subject related to molecular imaging of CAR-T cell therapy.
Figure 1. Cancer stratification by molecular imaging allows patients selection according to the expected outcome of a therapeutic approach by visualizing an expressed biomarker. The resulting patient subgroups can subsequently be treated with the most promising therapy.
Reference: Weber J,. Haberkorn U, Mier W. Int J Mol Sci 2015(16):4918-4946.