Daniel Aires, M.D.
Laird Forrest, Ph.D.
Background / Rationale- Triple negative breast cancer (TNBC), which accounts for 15-20% of breast cancers, lacks the hormone receptors that are used for targeted therapies; thus no targeted therapies exist. TBNC tends to metastasize (spread) more quickly and is more likely to recur (come back) after treatment. TBNC’s recurrent is thought to be determined by cancer stem cells (CSCs), which are a specialized group of cancer cells that are highly resistant to conventional chemotherapy and radiation. Therefore, targeting CSCs is of paramount importance to long-lasting TNBC treatment.
Project Description- Our product treatment is specifically designed to target CSCs in primary tumors and lymph node metastases (where cancers initially spread). Targeting of CSCs is accomplished by linking the widely used conventional chemotherapy cisplatin with nano-sized Hyaluronan, a natural compound in the body that cancers seek and bind. Hyaluronan is attracted to the CSC-expressed protein CD44, delivering cisplatin directly to CSCs. The HA-CD44 interaction, coupled with direct injection into tumors and accumulation of HA in local lymph nodes results in >100x more drug in tumors and local lymph nodes over traditional systemic delivery methods. Our drug is effective in all cancer models tested to date, including head and neck (pet dogs and lab mice), breast (mice), and melanoma (pet dogs and mice). In a clinical trial on pet dogs with spontaneous cancers (different university; we are not running that trial), our targeted chemotherapy successfully cured 3 of 7 dogs (43%) with squamous cell cancers. This compares with only 1/11 dogs (9%) treated with conventional chemotherapy at a much higher dose in a prior study by a different lab.
Objective- In this project, we will demonstrate that Nano Hyaluronic Acid Cisplatin (NHAP) is effective at treating human TNBC CSC tumors in mouse models.
Anticipated Outcomes- CSCs from TNBC patient-derived tumor samples will result in larger and more aggressive tumors in mice compared to non-CSC tumors. NHAP will reduce CSC tumor size and number of metastases compared to cisplatin treatment.
Impact on Human Health- This project will demonstrate that NHAP effectively kills CSCs from TNBC patient tumor samples in vivo. Development of NHAP may provide a targeted treatment for TNBC patients, over 46,000 cases per year in the US alone. In addition, CSCs are believed to be involved in most, if not all recurrent cancers; thus NHAP is a promising therapy in many other cancers as well.
Why is this important?
It will help develop a new type of treatment for hard-to-treat locally advanced triple-negative breast cancer by demonstrating potential efficacy of targeted platinum chemotherapy.
Who will benefit?
Patients with triple negative breast cancer. TNBC accounts for 10-20% of all breast cancer, which is millions of patients. In addition, CSCs are believed to be involved in most if not all recurrent cancers; thus our treatment may be effective in other cancers as well.