Targeted Therapies: What Can we Learn from Other Cancers?

Authors:

Jean-Luc Raoul, MD, PhD (France)

The demonstration of efficacy of trastuzumab in breast cancer and of imatinib in GIST more than 20 years ago was the first signal of a new revolution confirming that same pathological neoplasms can be extremely different molecularly. Currently these progresses are particularly obvious in breast, lung, colon cancers and melanoma. In breast cancers, previous therapeutic algorithms have been changed and are based exclusively on tumour expression of hormones and of HER2. In non small cell lung cancers, cancers with EGFR mutations (15% of the cases) and ALK translocations (5% of the cases) respond to EGFR TKIs (gefitinib and erlotinib) or to ALK TKI (crizotinib) and it is expected that in the near future most (?) of these patients can have a specific therapy guided by tumour genotyping. In advanced melanoma, activating mutation in BRAF are present in about 50% of the cases and in such cases the use of BRAF inhibitor improves outcome. In metastatic colorectal cancers, targeting EGFR in KRAS wt patients significantly improves response rate and survival. Currently some trials are comparing therapy based on tumour molecular profiling vs. conventional treatment in all solid tumours refractory to usual treatments. This new generation of biopsy-driven clinical trials will require the development early phases focused on the development of predictive biomarkers. In parallel another major progress is represented by non-invasive liquid biopsy allowing to study genomic evolution before and under treatment by sequencing tumour DNA into plasma. Preliminary results have shown that increase in plasma of mutant alleles is associated with emergence of therapy resistances, likely due to expansion of a resistant subclone.