ReviewClinical research in small genomically stratified patient populations

- Clinical research paradigm is shifting from 'histologically oriented' to 'molecularly oriented'.
- Clinical trials in patients with infrequent molecular alterations are specially challenging.
- Both Academia and Industry face common and specific problems in this subset of patients.
- Joint efforts have to be made to overcome difficulties in small genomically stratified patient populations clinical research.

The paradigm of early drug development in cancer is shifting from 'histology-oriented' to 'molecularly oriented' clinical trials. This change can be attributed to the vast amount of tumour biology knowledge generated by large international research initiatives such as The Cancer Genome Atlas (TCGA) and the use of next generation sequencing (NGS) techniques developed in recent years. However, targeting infrequent molecular alterations entails a series of special challenges. The optimal molecular profiling method, the lack of standardised biological thresholds, inter- and intra-tumor heterogeneity, availability of enough tumour material, correct clinical trials design, attrition rate, logistics or costs are only some of the issues that need to be taken into consideration in clinical research in small genomically stratified patient populations. This article examines the most relevant challenges inherent to clinical research in these populations. Moreover, perspectives from the Academia point of view are reviewed as well as initiatives to be taken in forthcoming years.