Successes and failures: Do targeted therapies live up to their promise?

ESMO teamed up with the European Association for Cancer Research (EACR) for a joint symposium to explore recent progress in the development of targeted therapies in oncology. The session provided a brief snapshot of just a few novel results in this exciting landscape.

Dr Pier Paolo Pandolfi of Harvard Medical School, Boston, USA, was certainly full of promise with his new concept of ‘pro-senescence therapy’. He discussed how a “deconstruction” of the molecular genetics human cancer led him to explore ways to trigger or potentate ageing, especially in cancer stem cells.

Sherene Loi from the Institut Jules Bordet, Brussels, Belgium, highlighted the high incidence of molecular aberrations associated with the phosphatidylinositol-3 kinase (PI3K) pathway in cancer. She presented the current status of various agents targeting this pathway (and potential resistance pathways) that are in Phase 1/2 development, and discussed who may stand to benefit from treatment with these novel agents based on our current understanding of the genetic and molecular profile of different types of cancer.

Professor Michal Neeman from the Weizmann Institute of Science, Rehovot, Israel, gave a presentation exploring the role of angiogenesis in cancer. He commented that the development of antiangiogenic therapy has become an especially popular field following the seminal work of Judah Folkman, and that the tight association between tumour progression and induction of angiogenesis is now widely recognized. However, he noted that targeting angiogenesis in cancer therapy has been relatively disappointing, and summarized the latest understanding about the role of hypoxia, vascular endothelial growth factor (VEGF) and the remodelling of the extracellular matrix in angiogenesis and tumour progression. He also emphasized that research should now focus more on the mechanisms by which tumours appear to escape antiangiogenic therapy.

Dr David Miles from the Mount Vernon Cancer Centre, Northwood, UK, also looked at the lessons researchers have learned from the ‘failure’ of antiangiogenic therapies to deliver on their initial promises. In indications such as renal cell cancer, where alterations in VEGF are regarded as the principle oncogenic driver, VEGF inhibition has led to clinically meaningful improvements in progression-free and overall survival, he notes, but in other malignancies the efficacy VEGF inhibition has been more modest. The lack of success of anti-angiogenic agents in the adjuvant setting is unsurprising too, given that micro-metastatic disease is unlikely to be VEGF-dependent. Echoing his fellow panelists, Dr Miles said that the legacy of Folkman would live on; anti-angiogenesis research had to continue, especially to find biomarkers for tumours most susceptible to this approach.