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We give – Dr. Erinn Rankin

We give – Dr. Erinn Rankin

July 22, 2020

Dr. Erinn Rankin
Imagine if we could improve patient outcomes by selectively eliminating the most aggressive cancer cells. Dr. Rankin and her team are working to develop novel therapies for advanced cancers. As a post-doctoral fellow, Dr. Rankin was part of the team that identified a link between the AXL signaling pathway and metastatic cancers including advanced breast, ovarian and kidney cancers. Dr. Rankin and colleagues showed that aggressive cancer cells that spread and are resistant to traditional chemo and radiation therapies increase the expression of AXL. Importantly, they showed that blocking the AXL pathway could reduce the size of multiple aggressive tumors. These studies provided preclinical evidence that led to ongoing clinical trials testing AXL inhibitors for cancer therapy. Dr. Rankin and her team continue to work on targeting AXL and other pathways that allow aggressive cancer cells to grow and survive. Please click here to see a description of some of the innovative projects ongoing in Dr. Rankin’s laboratory.

Reprogramming the immune system for ovarian cancer therapy.
Despite current surgical and cytotoxic therapies, 80% of patients diagnosed with advanced epithelial ovarian cancer (EOC) develop recurrent disease and only 30% of patients survive 5 years following diagnosis. There is an unmet need for effective therapies in the management and treatment of ovarian cancer. Dr. Rankin’s lab is working to develop therapeutic strategies for the treatment of advanced stage ovarian cancer and improve the overall survival of women suffering from this devastating disease.
This project is particularly exciting given that is has the potential to rapidly provide a new immunotherapy for the treatment of ovarian cancer. One of the key hurdles for cancer treatment is the ability of tumor cells to evade the immune system, thereby preventing the body’s natural immune defenses from destroying them. A prominent mechanism of tumor immune evasion is the establishment of an environment that is immunosuppressive and prevents strong T cell-mediated antitumor responses. Myeloid-derived suppressor cells (MDSCs) are immune cells with potent immunosuppressive activity. They are enriched in tumors where they promote immunosuppression, tumor cell survival, angiogenesis, and metastasis. Therefore, the ability to eliminate MDSCs in the tumor microenvironment is an attractive therapeutic strategy for cancer. Unfortunately, we lack good markers and ways to target MDSCs in cancer. Dr. Rankin’s group recently identified a cell surface protein that is highly expressed on the polymorphonuclear (PMN) set of MDSCs in both mouse and human cancers. Dr. Rankin is exploring the possibility of using antibodies that will bind to and deplete MDSCs expressing this protein as a therapeutic strategy for ovarian cancer therapy.

Increasing the efficacy and safety of radiation therapy for the treatment of ovarian cancer.
Radiation therapy plays a central role in curing cancer. Moreover, an emerging paradigm in cancer therapy is the use of radiotherapy to optimize antitumor responses to targeted immunotherapies. Radiotherapy can stimulate the immune system through the release tumor antigens and chemokines that promote antitumor immune responses. Clinically, the combination of radiation therapy and immunotherapy in patients with metastatic melanoma has led to durable systemic antitumor responses. However, the use of radiotherapy in the clinical management of ovarian cancer is limited due to the tumor spread throughout the abdomen and the potential for normal tissue toxicities associated with abdominal irradiation. Current research efforts within the radiation oncology field are focused on developing therapeutic approaches to maximize the therapeutic index of radiotherapy by enhancing the tumor response and protecting normal tissues from radiotherapy damage. Recently, strategies have emerged to protect normal tissues by delivering ultrahigh dose-rate irradiation (FLASH). Conventional radiotherapy delivers radiation at doses of 3-4 Gy/minute. In contrast, FLASH radiotherapy delivers doses at a dose-rate of 200 Gy/second. A recent study has utilized FLASH radiotherapy in preclinical models of lung cancer to demonstrate that FLASH radiotherapy significantly enhances the therapeutic ratio of radiotherapy in the lung by sparing normal tissues from irradiation-induced toxicity, while maintaining efficient lung tumor control. These studies suggest that FLASH radiotherapy may be an effective strategy to reduce the complications of radiotherapy while maintaining antitumor control. Dr. Bill Loo at Stanford has developed an experimental FLASH irradiator and has worked together with Dr. Rankin to show a dramatic reduction in radiation induced injury to the intestine. These findings raise the intriguing possibility that FLASH irradiation is an effective strategy to treat abdominal metastases from ovarian cancer and reduce the occurrence and severity of acute and late toxicities associated with abdominal irradiation. Moreover, Dr. Rankin is testing the combination of FLASH with immune checkpoint blockade as a safe and effective strategy to achieve durable responses in advanced ovarian cancer. Dr. Rankin believes that this novel therapeutic approach will be particularly useful for recurrent ovarian cancer patients whose tumors do not respond to current chemotherapy regimens.