Barcelona, April 11, 2014. Preclinical, translational and clinical researchers and physician-scientists from the Vall d’Hebron Institute of Oncology (VHIO) attended the Annual Meeting of the American Association for Cancer Research (AACR), celebrated this past week, 05 – 09 April in San Diego, California. During the meeting, Martín A. Rivas from VHIO´s Experimental Therapeutics Group led by Violeta Serra presented latest data from their lab.
Physician-scientist, Jordi Rodón, Principal Investigator of VHIO’s Early Clinical Drug Development Group and Medical Coordinator of the Research Unit for Molecular Therapy of Cancer – “la Caixa” (UITM), also chaired an AACR session on Novel Therapeutics as part of the Clinical Trials Symposia, which included two VHIO studies from the UITM and VHIO´s Clinical Research Program, directed by Josep Tabernero, exploring the use of two different FGFR (fibroblast growth factor receptor) inhibitors in metastasized solid tumors, particularly in breast and lung.
Both of these studies represent good examples of where personalized medicine in cancer is heading. For inclusion as candidates in these clinical trials, patients were pre-screened. Those patients whose tumors showed molecular alterations inhibited by these drugs, were consequently enrolled. The first study, presented by Rodrigo Dienstmann, who initially worked on the study as a senior fellow at the UITM and now continues this research at Sage Bionetworks, assessed a specific FGFR (fibroblast growth factor receptor) inhibitor for the very first time in humans. FGFRs play a role in cell proliferation and tumor cell survival, and genetic alterations of which may lead to the activation of this membrane receptor in various tumors.
This new inhibitor can be administered orally and has already shown important antitumor activity in patient-derived tumor xenograft (PDX) mouse models. The safety of this novel inhibitor was also assessed in this trial and the results show manageable side effects at doses producing therapeutic effects, enabling this new drug to enter into the next phase of research.
The second study, which also focused on another selective, potent FGFR (fibroblast growth factor receptor) inhibitor, assessed its safety and antitumor activity as a single therapeutic agent (with no concomitant medications). Again, thanks to VHIO´s pre-screening program, patients were identified as candidates for this study on the basis that their tumors contain the FGFR molecular alterations that may respond to this therapy. Importantly, antitumor activity was observed across multiple tumor types and the researchers also detected which may be especially sensitive.
Another study, presented as a poster, focused on the identification of biomarkers that predict sensitivity to a new therapy for luminal B breast cancer. This subtype of breast cancer is one of the most aggressive, for which there are no effective treatments available.
Therapies targeting the PI3K/Akt/mTOR pathway have been explored extensively over the last decade. Unfortunately, to date, many tumors only respond partially or even develop resistance to these therapies. Specifically, as established now for several years, blocking mTOR (an important pathway in survival, proliferation and cell metabolism) generates cellular changes that revert the effect of its inhibition through compensatory mechanisms. It has thus been proposed that one way of preventing this, is by simultaneously blocking the IGF-1 receptor. Early phase clinical trials have shown that this approach works in luminal B subtype tumors. Key to ongoing studies will be establishing how best to recognize which tumors will respond and those that will not.
Results from the Experimental Therapeutics Group presented at the AACR show that the capacity for response to a combined anti-mTOR/IGF-1R therapy resides in the expression of the IGR-1 receptor. These findings, when proven in patients, will provide us with a valuable tool at diagnosis, enabling us to recognize which patients will benefit from this treatment, thus providing a targeted therapy with less toxicity, better tailored to individual patients.
These studies all representative of VHIO´s purely translational approach to research aimed at realizing the true promise of personalized, ´precision´ medicine — turning discovery into more effective, targeted treatments and better practice for the care of our patients.