Rare cancers (defined as cancers of less than 6 /100,000 population per year incidence) are challenging to study and treat in the clinic due to their individual scarcity and potential clinical and molecular heterogeneity. As a result, the average outcome for patients with a rare cancer is inferior to those with more common cancers; collectively, rare cancers account for 22% of all cancer diagnoses, but 30% of cancer deaths. Patients with rare cancers need new approaches to treatment based on molecular features of their cancer, as evidence-based care is not usually available.
The WEHI Stafford Fox Rare Cancer Program (SFRCP) is a basic research platform for patients with rare cancers. Clinical data and tissue samples are collected from around Australia to facilitate the study of novel regulatory mechanisms found across rare cancers. Genomic analysis is performed for the majority of cases and when fresh tumour tissue is obtained, we endeavour to generate a patient-derived xenograft (PDX) model. PDX models allow treatment options matched to the genomic analysis to be investigated.
We have a cohort of 44 PDX models from 35 SFRCP patients covering 15 rare tumour types; including high grade serous endometrial cancer (n=5), ovarian carcinosarcoma (n=3), endometrial carcinosarcoma (n=3), uterine leiomyosarcomas (n=2), adenocarcinoma of cervix (n=2), adenosarcoma of the uterus (n=1), vulval squamous cell carcinoma (n=1) and large cell neuroendocrine tumour of the ovary (n=1). Molecular aberrations harboured by these PDX include mutations in BRCA1/2, BRIP1, AKT, PIK3CA; amplifications in CCNE1, MYC, EGFR; methylation of BRCA1 or RAD51C; mutational signature 3 (HRD); BRCA1 D11q expression and BRCA2 secondary mutations. A summary of the PDX cohort characterisation, including relevant drug response and relevance for patient outcome will be presented.