Biomarkerforschung bei Roche; Nr. 143

Therapy-oriented biomarkers are necessary in order to best adapt cancer therapies to the individual patient and to his or her disease. What is Roche contributing to this field?

Hot on the heels of cancer: biomarkers and combination therapies

Therapy-oriented biomarkers are necessary in order to best adapt cancer therapies to the individual patient and to his or her disease. What is Roche contributing to this field? What new diagnostic and therapeutic approaches are under consideration?

These questions were answered at the first Oncology Biomarker Symposium in October 2013 and in the subsequent interview with the organizer, Astrid Kiermaier, Associate Director, Oncology Biomarker Development:

Almost all pharmaceutical companies are nowadays carrying out biomarker research. Are we at Roche/Genentech really at the forefront of this field?

Yes! We begin the search for biomarkers very early in the research process and continue during the clinical trials and the approval process for a potential drug. At present, 70% of our cancer preparations are developed with a companion test featuring a companion diagnostic agent. These provide information on which patients are most likely to benefit from the drug. This is well above average for the pharmaceutical industry.

How are cancer patients currently diagnosed?

In the majority of cases, tumor-tissue samples are used for tumor classification and for subsequent therapy decisions. For example, the samples are examined to determine the presence and concentration of proteins which are characteristic of the particular cancer and diagnostically conclusive in respect of a therapy response to drugs. In addition, we collect blood plasma samples from patients in order to obtain genetic material from the tumor, i.e. DNA, which has been released into the blood by the tumor cells. Analyzing this circulating DNA allows us to predict the response to specific therapies and evaluate therapy resistances.

What form will cancer diagnostics take in the future?

Technology platforms, such as Next Generation Sequencing, which allow us to determine multiple markers simultaneously are beginning to dominate this field. It is anticipated that, in the next few years, this multi-parameter testing will replace individual marker identification using standard methodology. This represents a clear advance with regard to the information we are able to obtain from cancer patient tissue samples, which are often only available in small quantities. Future developments in cancer diagnostics and in cancer therapy will be driven primarily by increased understanding of the uncontrolled signaling pathways or immune processes in cancer patients.

Will signaling pathway-based therapies replace organ-specific cancer therapies as a consequence?

Signaling pathway-specific therapies would be ideal but biology teaches us otherwise. Firstly, it is important to understand whether a specific signaling pathway is, in fact, decisive in activating cancer growth. Although it was formerly believed that genetic changes in the tumor could be decisive in terms of therapy, we have however learned that anatomical origin is also a factor. For example, a drug administered as mono-therapy is highly effective in the case of malignant melanoma whose tumor cells exhibit the V600 mutation in the BRAF gene. In contrast, the same drug has little or no effect if this mutation occurs in colorectal cancer. We must discover the reason for this. Is the V600 mutation a definitive mutation in colorectal cancer or only one of many? Do we have to block two targets, i.e. two hyperactive signaling pathways at the same time? Our research is examining these issues.

Will there be more combination therapies in the future?

Yes, if treatments only intervene at one nodal point of a signaling cascade, other signaling pathways may be activated. Circumvention of the first block may render the treatment ineffective, again causing uncontrolled cell proliferation. It is therefore vital that we understand the biology of the diseases we want to treat, the decisive signaling pathways, the interactions between the signaling pathways and how these may affect the outcome of a therapy. This is an essential element of our biomarker program.

What are immune therapies in cancer?

Their objective is to boost or reinvigorate the host's immune response so the tumor cells can be destroyed. Tumors often develop mechanisms to circumvent the immune system which would otherwise destroy cancer cells.

How can biomarker research help in the development of these therapies?

Biomarker teams attempt to understand the actions of immune cells in the body of a patient or in a cancerous growth. In addition, we want to identify mechanisms for reinvigorating or generating an anti-tumor immune response. Biomarkers are used to understand the complexity of human cancer immunobiology and to identify patients who are likely to benefit from immunotherapy.

Why are all potential cancer drugs not developed using a companion diagnostic test?

We do, of course, want to develop all our drugs using a companion diagnostic test. That is our primary objective. However, the biology of the disease can be so complex that it is not possible for us to identify a biomarker suitable as a companion diagnostic agent, if the approval-related studies begin with the candidate pharmaceutical. In these cases, we continue biomarker research until the pharmaceutical has been approved. There are however cases where we do not need a companion diagnostic test because the drug is highly effective against very specific diseases.

Why do we need biomarker studies that go beyond the development of a companion diagnostic agent?

Biomarker studies can help to promote understanding of the biology of the disease and identify those patient sub-groups in most urgent need of a treatment. Biomarkers also help us understand the results of combination therapies and identify how best to combine pharmaceuticals. A further goal of biomarker research is to understand the development of resistance to cancer therapies. If nothing else, an effective new biomarker should be much better than traditional clinical studies, such as x-ray, at telling us whether a pharmaceutical is effective.