The performance of translational research often means bringing together very different ways of thinking from preclinical and clinical team members. Even common terms can have different meanings for clinicians and biologists. As a result, some interdisciplinary meetings involve “translation” in the literal sense—explaining terminology, concepts, and context across disciplines. In many cases, a translationally trained biologist or clinician plays a key role in helping both sides to understand each other.

Many promising translational research ideas get bogged down not because of scientific flaws, but due to organisational or communication issues. Too often, teams realise only at the end of a project what should have been discussed during the planning phase. Researchers trained in translational science understand both “worlds” and both “languages” and can help to translate ideas so that clinicians and biologists share a common understanding of the project goals and limitations.

To reduce the risk of failure, there are important questions that biologists should ask clinicians—and clinicians should ask biologists—right at the start of a project. A crucial point is to involve both disciplines early, instead of designing a project within one field and adding the other at a later stage.

Some key questions that should be addressed in the early planning phase are summarised in Figure 1.

In our projects, we have encountered several challenges that could only be solved through close discussion and cooperation between the clinical and experimental sides. Below are examples.

• Biologists received “glioblastoma” samples from the neurosurgical operating room without realising that definitive histological results would become available only about 10 days later. As a consequence, in the initial phase, samples included metastases from other cancers, IDH-mutated low-grade gliomas, and re-resections after prior radiochemotherapy. Only after a few months did a clinician go through the neuropathological reports and exclude samples.
• In a planned project on circulating-tumour DNA (ctDNA) that involved blood samples from patients undergoing radiochemotherapy, clinicians suggested the inclusion of 20 patients with 10 time points—without being aware of the substantial costs associated with ctDNA analysis for each sample. The biologists who were involved from the start were able to explain this issue, and the sample size was adjusted to 10 patients and three time points.
• In articles that have been published in some high-impact publications and that involve analysis of molecular prognostic markers, clinical datasets have been combined that, from a clinician’s perspective, represent distinct tumour entities with different prognoses and treatment strategies. In addition, prior radiotherapy and/or chemotherapy before surgery is not always considered or even reported.

At the same time, our group has also seen how powerful true interdisciplinary collaboration can be, as shown in these examples.

• After characterising glioblastoma stem-cell-enriched cultures, we correlated the biological findings with patient outcomes, including recurrence patterns. Notably, matrix invasion in vitro was associated with multifocal recurrence in patients.
• In a follow-up study, stem-cell properties that were observed in vitro were linked to volumetric parameters from preoperative MRI scans.
• For a project on immune-cell infiltration before and after radiotherapy, we selected a cohort of patients with soft-tissue sarcoma because their biopsy material was well-suited to translational analyses. From an initial cohort of more than 100 patients, about 20 were chosen for multiplex immunofluorescence due to limited time and funding. Patients were carefully selected based on clinical characteristics and tissue availability, and sections were annotated by expert sarcoma pathologists before analysis. Despite the small cohort, this well-planned approach allowed us to demonstrate a clear prognostic impact of immune-cell infiltration.

In summary, it is essential to involve both clinical and experimental expertise early in translational research to avoid seemingly simple mistakes that can seriously affect data quality and interpretation. Far from being a burden, truly translational projects are often the most rewarding, as they offer exciting insights and real benefits to both disciplines.

Associate Professor Dr Franziska Eckert

Medical University of Vienna

Comprehensive Cancer Centre Vienna

Austria