MRA awarded three researchers with pilot awards, $100,000 over two years, to pursue first-of-its-kind approaches to melanoma prevention and treatment.

• Dr. Sancy Leachman, University of Utah
  Proposal Title: Sulforaphane, a melanoma prevention agent for high-risk MC1R genotypes
  

  Leachman

  
  It is now known that the cancer prevention agent sulforaphane has the potential to compensate for the defective response to ultraviolet light that underlies the increased risk for melanoma suffered by individuals with fair skin and red hair. Dr. Leachman will use this discovery to design and carry out a clinical study with human tissues that will provide information needed in order to decide if this agent merits advancement to a clinical trial for prevention of melanoma in this high-risk population.



• Dr. Maria Wei, North California Institute for Research and Education, University of California San Francisco
  Proposal Title: Mechanisms of melanoma treatment resistance
  

  Wei

  
  Melanoma is an aggressive cancer of the skin and eyes that has a high tendency towards metastatic behavior. The incidence of this malignancy is rising, in marked contrast to the declining incidence of other, more common cancers. There has been no breakthrough development in melanoma therapeutics for more than 25 years, and currently there is no effective treatment for metastatic disease. Recent studies from this laboratory have demonstrated that melanoma sensitivity to chemotherapy treatment is influenced by a pathway that regulates the formation of a compartment found in melanomas, called melanosomes. Normally, the pigment melanin (which gives rise to the color found in the skin, eyes and hair) is synthesized and stored within melanosomes and then (in the skin) is secreted, and taken up by neighboring cells called keratinocytes. Dr. Wei found that mutations in genes resulting in aberrant melanosome formation also cause increased melanoma sensitivity to a variety of chemotherapy agents, suggesting that melanosomes may play a fundamental role in melanoma chemosensitivity. In these proposed studies, Dr. Wei will investigate what role these genes, known to regulate melanosomes, play in chemotherapy resistance and how they could be targeted for the development of novel melanoma therapies.



• Dr. Xue-Zhong Yu, Moffitt Cancer Center
  Proposal Title: Treatment of established melanoma by tumor-specific Th17 cells
  

  Yu

  
  Tumor-specific CD8+ cytotoxic T lymphocytes have been the focus for the lymphocyte-based cancer immunotherapy; however the complete tumor regression has been achieved in only a minority of melanoma patients. Recent evidence indicates that CD4 T cells may be a determining factor in promoting or inhibiting anti-tumor responses through T helper cells or regulatory T cells, respectively. Dr. Yu's laboratory as well as others discovered that Th17 cells, a newly defined T helper subset, are highly effective in eradicating tumors once they are directed to tumor associated antigens. Dr. Yu will further study the potential of Th17 cells in cancer immunotherapy in the combination of myeloabliative bone marrow transplantation. The proposed strategy utilizes the advantages of host lymphocyte depletion, hematopoietic stem cells, and redirection of T cell specificity to endogenous melanoma-associated antigen. The proposed study is expected to establish a novel strategy to treat established melanoma in preclinical models that may be readily applicable in clinic.