Personalised healthcare inconceivable without biomarkers

 As objective parameters, they identify disease-specific processes or monitor the course of treatment.

In addition to promoting an exchange of expertise, the main goal of the Oncology Biomarker Symposium was to grow a network across functions, divisions and geographic sites. Biomarker tests can only parallel drug development and, ideally, be launched alongside treatments if Pharmaceuticals and Diagnostics work closely together.

Why is personalised healthcare so important? “Quite simply,” said Daniel (Dan) O’Day concisely and pragmatically in his welcome address, “because it makes sense. It makes sense not only from the patients’ perspective, but also from a scientific and economic standpoint.” In the long run, he added, no company can afford to make expensive, innovative products that are effective only in some of the patients who take them. The one-size-fits-all mentality under which medicines are broadly used to treat lung or breast cancer is no longer viable. Astrid Kiermaier, the symposium organizer from the Basel Oncology Biomarker Development Team, says that treatments have to be adapted to patients nowadays, not the other way around.

The potential clinical applications for biomarkers are many and diverse. There are specific indicators for assessing a person’s risk of developing a particular type of cancer, or for determining cancer subtypes.

It makes sense from a patients’ perspective but also from a scientific and economic standpoint.
Daniel O’Day

Companion diagnostic tests can be used to identify patients with a high likelihood of responding to a particular treatment. Biomarkers can also deliver information on the progress of treatment, side effects and resistance, ideally before such changes are clinically apparent.

Biomarker identification is at an advanced stage. However, without clinical validation—for example if no treatment is as yet available—a biomarker is useless. It will only be licensed for routine use if it facilitates assessments that improve the treatment patients receive. In addition, precise, reliable tests are required for each biomarker. False negative or false positive results often mean that patients don’t receive the necessary treatment, or that they run the risk of unnecessary side effects.

Today, therapy-indicating companion diagnostics is mainly carried out sequentially with tissue samples, which, however, are in limited supply. Increased use is therefore being made of multiplexing technologies to identify different biomarkers simultaneously in parallel tests.

Tissue samples can only ever provide a snapshot of a specific area of a tumor. Neither treatment progress nor the heterogeneity of a tumor can be decoded from tissue. For this reason, companion diagnostic tests will focus more in the future on tumor cells circulating in the blood or on their DNA. This would enable the early recognition of potential resistance, for example.

Biomarker or technology—which is more important in the development of therapy-indicating diagnostics? This is the wrong question to ask; the one is of no use without the other. Close links between the different functions and divisions is therefore essential. Thanks to the symposium, at least the people working on oncological biomarkers at Roche have moved a little closer together.

It’s all a question of taste

Seeing the expressions on the faces of the people taking part in the biomarker experiment with phenylthiocarbamide (PTC) was sufficient to answer this question. While some of the testers (the supertasters) screwed up their faces in disgust, others (the nontasters) remained relatively indifferent.

The reason? Supertasters experience the sense of taste with far greater intensity. This is especially true of the bitter-flavored PTC mentioned earlier, which only two thirds of all people can taste. Roche employees fit the average demographic in terms of taste. About 35% are supertasters, 35% tasters and 30% showed no reaction at all to the acrid substance. There’s no accounting for taste, as everyone knows. But it’s a lesser known fact that this is scientifically verifiable. Our sensitivity to taste is all in our genes. How strongly we react to the bitter PTC is determined largely by the TAS2R38 gene, also known as the “PTC gene,” and its two variants.

To taste or not to taste? The more taste-sensitive among us usually find cigarette smoke or Brussel sprouts unpleasant. So next time you see a co-worker lining up for Brussel sprouts in the staff restaurant, you can be fairly certain that this person is a non-taster. And don’t scold your kids for refusing to eat their sprouts. It’s all in the genes. They just happen to be supertasters.

Treating patients who will benefit

Biomarkers and associated personalised healthcare tools are used to treat cancer more often than other conditions. There is a whole range of measurable parameters that deliver useful information for the purpose of identifying the cancer subtype or tracking tumor development. It is no accident that biomarkers play such a pioneering role in oncology. The side effects of cancer therapy can be consid­erable, so it is important to limit treatment to patients who will benefit. To date, 18 companion diagnostic tests have been approved, some of which target the same biomarker, such as the HER2 protein.

A glimpse at the research and development pipeline brings home just how important personalised healthcare is at Roche and Genentech:

  • 5 out of 9 oncological products are prescribed on the basis of companion diagnostic tests.
  • Currently, more than 30 non-redundant companion assays are in the clinical development and post-marketing stages.
  • There are companion tests for 70% of all substances in clinical development.

Tags: Sustainability, Innovation, Science