Professor Peter Hersey - Selected Publications

Hersey’s work on apoptosis showed that TRAIL killed melanoma by the intrinsic mitochondrial pathway and involved an alternate pathway involving a newly described molecule called Smac/DIABLO. Insights from these studies have been invaluable in helping to understand the induction of apoptosis by chemical agents such as Staurosporine and histone deacetylase inhibitors.

The notion of immune reactivity to malignancy especially melanoma has stimulated much research.  The mechanisms of tumour evasion still remain elusive but this seminal paper describing a defect in the JAK-STAT pathway which results in the resistance of melanoma cell lines to interferon. The results of this study indicated a defect at the level of STAT1 may be a general phenomenon responsible for reduced cellular responsiveness of melanomas to IFNs

The cytotoxic mechanism involved in CD4 T-cell killing of melanoma cells and, in particular, the role of FasL/Fas interactions in this killing is considered to be an important aspect of protection against the development of skin malignancies. How this mechanism is orchestrated remains unclear.  This paper showed that the CD4 T cells induced apoptosis in autologous melanoma cells by MHC-restricted mechanisms but lysed an allogeneic melanoma cell by a non-apoptotic mechanism. Melanoma cells expressed both Fas and FasL, but killing of melanoma cells did not involve Fas/FasL interactions. This observation lead to the recognition that the TRAIL ligand induced apoptosis in melanoma cells via the intrinsic mitochondrial pathway.

The results of this report suggest that PCR with MART-1 and with tyrosinase identifies subgroups of patients who develop disseminated or locally recurrent metastases. This was further investigated and it was revealed that immune responses against MART-1 may reduce the establishment of disseminated metastases.  An extremely important finding in relation to our understanding of why some melanoma patients succumb to their disease very rapidly.  The identification of subgroups of patients is key to developing personalised medicine.

Esteem Factors

• Editorial Board Member for the journals Melanoma Research and Cancer Immunology & Immunotherapy. He is also Associate Editor for Journal of Immunology. Hersey took part in the Editorial Review Panel for Cancer Research, International Journal of Cancer, Oncogene, Clinical Cancer Research, Journal of Investigative Dermatology and others. Finally he is an Invited Member for the WHO Melanoma Program Committee.
• Since 2000, Hersey has participated in a number of international trials and was invited by Genta/Aventis to be an advisor for their submission to the Oncology Development Advisory Committee. He has also been invited to Medical Advisory Committees for future trials planned by Pfizer, MedImmune and Medarex/Bristol Myers.
• Hersey has been a member of the National Ranking Committee (Experimental Therapy) for state cancer councils for the past four years and have participated in the National Health & Medical Research Council (NHMRC) Project Grant Assessment Committee, as well as review of many grants for the NHMRC applications. He has been on the Board of the Society of Biological Therapy for four years and remains on the Meetings Committee for the Society for Melanoma Research.
• Since 2000, Hersey has published 36 peer reviewed articles, including 4 invited reviews. Twelve of these are in journals with impact factors greater than 6.4 and includes an article in Nature Reviews Cancer. He is first author on 8 publications and senior author on 25. His articles on TRAIL induced apoptosis were well ahead of similar studies in other cancers and since then he has taken a leading role in delineating resistance mechanisms to apoptosis as a way forward in developing new treatment approaches for melanoma.
• Hersey has been a panel member on the National Cancer Council Ranking Committee for Experimental Therapy for the past 4 years and Co-Chairman of this panel in 2004.  He is a member of the Grant Review Committee for the “Cure Cancer Australia” organisation.Hersey was on the Board of the International Society for Biological Therapy and recently have been appointed to the programs Committee of the newly created Melanoma Research Society. He was Chairperson for the Melanoma and Skin Cancer Group of the Clinical Oncology Society of Australia until 2003.