September 2014 Edition Vol.11, Issue 9

Evolution of Angiogenesis Biomarkers: What the Future Holds

Evolution of Angiogenesis Biomarkers:
What the Future Holds (continued)

Furthermore, the results from a Phase 2 trial presented at ASCO 2014 in patients with ovarian cancer, who had not received prior anti-angiogenic therapy in the recurrent setting or prior PARP inhibitors, demonstrated a median PFS of 17.7 months in those treated with the combination of cediranib and the PARP inhibitor, olaparib, in comparison to 9 months with olaparib alone.19 Blood samples from a subset of 13 patients in this trial were subjected to biomarker analyses at baseline and day 3 of treatment. CECs, CEPCs, and plasma cytokine (IL-6, IL-8, VEGF and soluble VEGFR2) levels were measured. The olaparib-cediranib combination treatment caused a greater decrease in IL-8 and a median 3.5 fold increase in CECs when compared to treatment with olaparib alone; the increase in CECs was significantly correlated with PFS>6 months in 6 patients on the combination arm. 

These highly promising results make cediranib an interesting candidate for ovarian cancer treatment, and suggest that the identification of biomarkers to identify appropriate patients for treatment and to follow their responses may improve patient care. It has also been proposed that such strategies in other types of cancer, including non-small cell lung cancer and colorectal cancer, may offer predictive power to identify patients that are most likely to respond to treatment.20, 21

What the Future Holds:

For decades, the role of angiogenesis in cancer has intrigued researchers and clinicians. There have been some significant breakthroughs with drugs like bevacizumab and some of the TKIs that have anti-angiogenic properties, but a means by which to predict which patients will respond remains elusive. Researchers have discovered novel mechanisms of manipulating the process of angiogenesis via the discovery of connections between angiogenesis inhibition and immune modulation; these mechanisms can be further exploited to discover effective combination therapies.

In addition, new biomarkers have been identified that may predict efficacy of therapy. However, there are likely multiple biomarkers and complex pathways involved in angiogenesis, and it will require many more years of research to elucidate these complex mechanisms. Moreover, it will be essential to better understand the mechanism of action and toxicities of anti-angiogenesis agents and identify sub-populations of patients across cancer types that will respond to therapy with tolerable toxicity.

In recent years, new angiogenesis biomarkers have been discovered, and are now the focus of a growing number of research efforts.  There has been much progress both in biomarker discovery and therapeutic development. Additional study of the interface between angiogenesis and the immune microenvironment represents a particularly promising direction. Together, these novel therapeutic approaches and the advanced understanding of the complexity of anti-angiogenic biomarkers will likely transform the way we target angiogenesis, and help deliver more personalized approaches to the use of these drugs in cancer treatment.

About the Contributor

Chief Medical Officer and Founder, N-of-One, Jennifer Carter, MD has been an early driver in shaping and delivering personalized medicine for oncologists at the point of care. Today, N-of-One is the leading provider of molecular interpretation and therapeutic strategies for oncology.



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