Despite recent advances in therapies for breast cancers, nearly half a million women die of this disease annually worldwide. While ovarian and endometrial cancers are less frequent than breast cancers, nearly 65% of women with ovarian cancer die from this disease and women diagnosed with advanced stage endometrial cancers also have very high mortality rates. Recent studies indicate that these three cancers have in common frequent mutations in a set of genes that regulate a cancer pathway, called the PI3K pathway.
The scientists who have been assembled for the Stand Up to Cancer - PI3K Dream Team in Women’s Cancers are the pioneers who discovered the PI3K pathway and who have validated its role in human cancers. Based on the research of these scientists and clinicians, pharmaceutical companies have developed inhibitors of the PI3K pathway that are entering clinical trials at the affiliated institutions (Dana Farber/Harvard Cancer Center, Memorial Sloan-Kettering Cancer Center, M.D. Anderson Cancer Center, Vanderbilt-Ingram Cancer Center, Herbert Irving Comprehensive Cancer Center, Vall d’Hebron Oncology Research Institute, and Massachusetts General Hospital).
However, as with other ‘targeted therapies’ it is likely that only a fraction of patients who go on trials with PI3K pathway inhibitors will benefit from these drugs. If it is not possible to predict ahead of time which patients will benefit, then many women will be given therapies that provide no benefit or that cause unnecessary complications. Importantly, the time required for approval of the drugs will be much longer and the availability of drugs for patients who could benefit will be delayed.
The goal of this Dream Team is to discover approaches that will predict the patients who will respond to PI3K pathway inhibitors; thereby, accelerating drug approvals and ultimately providing techniques for personalized cancer treatment that can be incorporated into standard practice.
Our Dream Team has a deep understanding of the PI3K pathway and we have developed preliminary data that suggests how to predict patients whose tumors are likely to respond to PI3K pathway targeted therapies based on mutational events in the tumor or imaging approaches such as FDG-PET. Our challenge is to test these ideas in ‘proof of concept’ clinical trials. The members of this Dream Team have already shared their unpublished data on the mutational status of components of the PI3K pathway from over 1,200 breast tumors, over 500 ovarian tumors, and over 250 endometrial tumors. We are assembling an inter-institutional database that correlates the mutational status of this pathway with pathology, PET imaging responses and patient outcomes in multiple ongoing clinical trials. This unprecedented level of collaboration across the top cancer centers in the US and worldwide was encouraged by formation of this Stand Up to Cancer Dream Team.
One of the hypotheses being tested by this team is that since PI3K pathway mutations are frequent in breast, ovarian and endometrial cancers, a common set of techniques may be successful at predicting patients who will benefit from PI3K pathway inhibitors in all three of these diseases. Thus, we are taking the unprecedented approach of not only collaborating across multiple institutions but also across multiple diseases. Our hope is that by facilitating the exchange of materials and ideas between scientists and clinicians working in these three diseases, we will accelerate the cure of all three.