The CARE Fund sets the stage for novel research efforts that can generate or accelerate the next big discovery in cancer research. The Breakthrough Research Program seeks to provide seed funding for innovative, cross-disciplinary research and collaborations that aim to find the next big discovery in cancer research.

Recombinant Epithelial Junction Opener Protein for Enhanced Drug Penetration in Epithelial Tumors

University of Washington (Principal Investigator: Andre Lieber, MD, PhD)

This proposal aims to break down a major barrier to treating ovarian cancer. Recurrent ovarian cancer is often resistant to treatment because chemotherapy drugs, such as Doxil, penetrate tumors poorly. This means that more distant tumor cells receive low drug concentrations and survive chemotherapy. One of the reasons for poor drug penetration is that tumor cells form a barrier of tight junctions. We have developed a small recombinant protein to open tight junctions and allow greater accessibility of chemotherapy molecules. When we tested our junction openers (“JO”) along with chemotherapy drugs in mice, we were able to completely eliminate the tumor in most animals. We also demonstrated excellent safety of this approach in monkeys when we tested JO in combination with Doxil at doses that we would use in patients. We propose a phase I/II clinical trial with JO and Doxil in women with recurrent ovarian cancer. The primary goal of this trial is to confirm the safety of the treatment and evaluate therapeutic responses. Furthermore, we will use serum samples and, if available tumor biopsies, to learn more about the interaction of JO with the body and the tumor. We expect to demonstrate that the treatment is safe with increased efficacy of Doxil treatment. This new approach will not only result in better outcomes for ovarian cancer patients but can also potentially be expanded to treat other patients with solid tumor cancers.

Proactive Cancer Immunotherapies for Initial and Recurrent Disease

Institute for Systems Biology (Principal Investigator: James Heath, PhD)

For in-remission cancer patients, recurrent disease is often metastatic with few viable treatments. A major challenge is that recurrent cancer is often not detected until it is metastatic, and surgical resection of metastatic disease is typically not practical. However, early signatures of recurrent disease can be detected in the blood. Furthermore, a genetic analysis of the patient’s primary tumor can inform the design of a personalized cancer vaccine that is engineered to specifically activate tumor-killing T cell populations. Thus, the combination of early detection of recurrent disease (prior to the emergence of clinical symptoms) through a deep molecular phenotyping of the patient, coupled with proactive vaccine strategies, provides the opportunity to significantly reduce the chance of disease recurrence. The technical challenges associated with taking advantage of this opportunity are daunting, but we have assembled a team of world leading investigators from across the disciplines of computer science, bioengineering, cancer biology, and clinical cancer care to achieve this goal. This proposed program initially formalizes early detection strategies through deep characterizations of patients with ovarian, breast, and colorectal cancers, prior to selecting a set of cancer patients for clinical trial designed to intercept recurrent disease through the design and administration of personalized, tumor-specific vaccines.