1. Summary of programme area and objectives1. Summary of programme area and objectives

1.1 Cancer chemotherapy cures some patients, but response rates remain disappointing for many solid tumours. This is particularly true of rare tumours, such as ocular melanoma. Part of the explanation for this is tumour heterogeneity: responsiveness to individual chemotherapeutic agents varies widely between tumours of the same histological type. This heterogeneity is present at the molecular, cellular, histological and clinical level - in many respects cancers are as different as their owners. Patients therefore stand to benefit considerably if their treatment can be individualised.

1.1.1 Development of ATP-based chemosensitivity assays
1.1.2 Development of new chemotherapy regimens, particularly for ocular melanoma
1.1.3 Trials of assay directed chemotherapy in ovarian cancer and melanoma
1.1.4 The molecular basis of eye melanoma
1.1.5 The role of new blood vessel formation in tumours and the eye

  2. Programme plan

2.1 Uveal melanomas are the most common primary intraocular malignancy in adults and pose a significant threat with approximately 50% of patients ultimately dying from their disease. In the past two decades there has been considerable progress in developing therapeutic options that avoid the need for removal of the affected eye. Whilst this has, in many cases, led to the preservation of a cosmetically acceptable eye and/or useful vision there has been no impact on patients' survival. The identification and treatment of high-risk patients with adjuvant therapy at the time of their initial diagnosis may ultimately lead to improved survival in these patients.

2.2 In the last few years certain cytogenic abnormalities have been detected within uveal melanomas and these have been found to have a profound prognostic significance. Further research is directed into the characterisation of these and other abnormalities within the tumour genome. Increasing our understanding of the molecular genetic events that lead to the genesis of these tumours may provide us with greater means for identifying high-risk individuals. In addition, an increased understanding of the molecular mechanisms responsible for the development of these tumours may provide us with opportunities to control tumour growth at a molecular level.

2.3 Adjuvant therapies must be developed to address the problem of micro-metastatic disease present at the time of primary therapy. Such therapeutic options may include: immunotherapy, anti-angiogenic therapy, chemotherapy and gene therapy.

2.3 Retinoblastoma is the commonest intraocular tumour in childhood with a frequency of approximately 1 in 20,000 - 1 in 30,000 live births. Present treatment is highly successful in controlling the primary tumour and survival rates in affected children are extremely high. Primary treatment that may include radiotherapy, laser therapy, cryotherapy and chemotherapy may have a secondary adverse affect on visual function. Future treatment strategy will aim to eradicate the primary tumour, but at the same time minimise normal tissue damage. Again, in recent years there has been

a considerable increase in our understanding in the genetic and molecular events that determine the development of retinoblastoma. Future research should be directed at increasing our understanding of these molecular genetic events that in turn may provide us with therapeutic options for eradicating the primary tumour with a minimal disturbance of normal tissues.

  3. Future development work in the programme during 2002/3

Research Priorities

3.1 Epidemiological and Service Issues

· The epidemiology and risk factors for ocular and adnexal tumours

3.2 Clinical and Laboratory Issues

· Research into the mechanisms of tumour induction