An important benefit of the tremendous progress in stem cell research has been the recognition that stem cell pathways are frequently re-activated in cancer cells conferring stem cell-like properties on a subset of tumor cells. This understanding is the basis for the emerging field of cancer stem cell (CSC) research.
The cancer stem cell paradigm is a new approach in cancer research that has profound implications for new anti-cancer drug development. It is now widely understood that tumors are comprised of different cell types. Experimental evidence has accumulated from many laboratories indicating that different tumor cells vary dramatically in their ability to grow a new tumor. The tumor cells capable of re-growing a new tumor are the CSCs, whereas the bulk of the tumor cells lack this capacity. This property of seeding new tumor growth is analogous to the growth of distant metastases that is a major cause of mortality in cancer patients. The highly tumorigenic CSCs share certain properties with normal stem cells, but have accumulated cancer causing mutations clearly making them abnormal. It is now widely appreciated that many current therapies fail to effectively target the CSC population, and thus the CSCs mediate recurrence of disease after treatment. New drugs that target CSCs to kill them or cause them to differentiate into less dangerous, non-tumorigenic cells have the potential to provide significant benefit to patients and to dramatically improve cancer treatment.
This project is focused on developing a new anti-cancer drug with an exciting strategy to rapidly identify the specific tumor types that would most benefit and accelerate the process of evaluation and approval in breast cancer. Our drug has been shown to effectively block CSC self renewal in a variety of common types of cancer. New therapeutic agents that are effective in targeting cancer stem cells may reduce metastases and relapse after treatment thus providing a chance for improved long term survival of cancer patients. In the first phase of the project, we will complete the manufacturing of the drug for subsequent use in clinical trials and also execute safety studies that are necessary before initiating clinical trials. Next, we will test the safety of the drug in Phase 1 clinical trials. Lastly, we will determine the efficacy in breast cancer patients in Phase 2 trials. This project will utilize innovative clinical trial designs to identify the patient populations most likely to benefit from treatment with our new drug. We intend to focus our clinical testing on an important subset of women with breast cancer for whom effective therapies are currently lacking. Our project is a unique partnership of industry and academic researchers and clinicians dedicated to bringing new medicines to treat patients most in need of effective therapy. This program is designed with input from the FDA to potentially support efficient regulatory approval.
Statement of Benefit to California:
Although tremendous advances have been made in the treatment of breast cancer, this disease remains a significant public health problem and is a leading cause of death in women ages 20-59. Recent research has led to the understanding that breast cancer is a heterogeneous set of diseases that can have very different prognoses. For example, the basal and triple negative subtypes of breast cancer have been found to be relatively resistant to current therapies and frequently spread to distant sites in the body. This project is focused on developing and testing a new therapeutic which targets a key pathway shown to play a significant role in these difficult to treat forms of breast cancer. We are developing unique strategies and technologies for the early detection of breast cancer in patients with poor prognoses and who would benefit from this therapy. Furthermore, our work has provided unique insights into identifying the individual patients who have the highest likelihood of responding to this therapy and is a clear example how “personalized medicine” is becoming a reality in cancer research and drug discovery.
This treatment attacks cancer stem cells, the subset of tumor cells that mediate resistance to conventional cancer therapies such as chemotherapy and radiation that results in disease recurrence after treatment. Thus, this project will provide funds for creation of a new medicine that will target women in need of new therapeutic options. Cancer stem cells are also thought to mediate disease progression and the spread of metastasis. Our new agent reduces cancer stem cell frequency, tumor recurrence and the spread of metastatic disease in pre-clinical cancer models. Patients with advanced, metastatic cancer typically require lengthy, expensive hospitalization. This drug may reduce the incidence and relapse of metastatic cancer, thus reducing hospitalization and associated specialized care for advanced cancer patients.
In addition to the medical benefits derived from the development of a new therapeutic agent, funding this project will create and maintain high quality jobs in the state of California both in the private and public sectors. Our California-based team includes expertise in drug development, stem cell biology, early and late stage clinical trials, and is a synergistic partnership among researchers in industry, academia and community medicine within California. Funds from this project will support research efforts and clinical testing at several sites throughout the state.