Jorge Reis-Filho graduated from medical school at Universidade Federal do Parana, Brazil in 1999 and holds a joint medical degree from University of Porto, Portugal. After finishing his histopathology training at the Institute of Molecular Pathology and Immunology, University of Porto, Portugal, in 2002, he started his PhD on breast cancer molecular pathology at the Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK, under supervision of Professor Sunil Lakhani and Professor Alan Ashworth. Dr Reis-Filho was appointed the Team Leader of the Molecular Pathology Team at the Breakthrough Breast Cancer Research Centre in January 2006. In 2007, Dr Reis-Filho was awarded the CL Oakley Lectureship by the Pathological Society of Great Britain and Ireland and was the recipient of the BACR Translational Research Award. Dr Reis-Filho is the youngest ever Fellow of The Royal College of Pathologists to have become a member by published works. He is the associate editor for molecular pathology of The Journal of Clinical Pathology, and a member of the editorial boards of The Journal of Pathology, Laboratory Investigation, The International Journal of Surgical Pathology and of the international advisory board of the Archives of Pathology and Laboratory Medicine.

Dr Reis-Filho’s research programme focuses on the development of an integrated morphological and molecular classification for breast cancer and identification of novel therapeutic targets for specific subgroups of breast cancer patients. Dr Reis-Filho has either initiated or been directly involved in collaborative research endeavours that have led to the characterisation of the pathological features, molecular profiles and prognostic implications of basal-like and triple negative breast carcinomas and the extent of their biological and clinical overlap.

In collaboration with the Breast Cancer Linkage Consortium, Dr Reis-Filho has validated the association between BRCA1 germline mutations and the development of basal-like and triple negative breast carcinomas. His group has also demonstrated that BRCA1 pathway is dysfunctional in a subgroup of sporadic basal-like and triple negative cancers and characterised the mechanisms leading to inactivation of this pathway in sporadic breast cancers. Furthermore, in collaboration with Professor Ashworth’s group, he characterised the histopathological and molecular features of a conditional mouse model that demonstrated directly that Brca1 and Trp53 inactivation in the mouse mammary gland leads to the development of basal-like and triple negative cancers, often with metaplastic features. In conjunction with the body of work generated by Alan Ashworth’s group, the results of Dr Reis-Filho’s research endeavours have paved the way for clinical trials with Poly ADP Ribose Polymerase (PARP) inhibitors in cancer patients with germline BRCA mutations, as well as patients with triple negative breast cancers. The results of the phase I and II trials appear to support the hypothesis that these patients may indeed benefit from PARP inhibitor-based therapy. Dr Reis-Filho’s team has also helped define a novel mechanism of resistance to chemotherapy and tailored therapies in tumours from patients with BRCA2 germline mutations, which has yielded not only new insights into the genetic basis of targeted therapies but also evidence of interaction between clonal evolution and selective pressures in human cancers following a Darwinian model.

To understand the genotypic-phenotypic correlations in breast cancer, Dr Reis-Filho’s group has applied high throughput methods to unravel the molecular underpinning of special histological types of breast cancer. This work has demonstrated that pleomorphic lobular carcinomas evolve through the same genetic pathway as classic lobular cancers and that their higher nuclear pleomorphism and reported more aggressive clinical behaviour may stem from the acquisition of amplification or deletion of specific oncogenes or tumour suppressor genes, respectively, and that invasive micropapillary cancers consistently display a luminal phenotype and harbour a specific constellation of genetic aberrations. In addition, Dr Reis-Filho’s group has defined the transcriptomic similarities between hyper-cellular mucinous cancers and neuroendocrine carcinomas. Dr Reis-Filho’s studies on metaplastic breast carcinomas have demonstrated that these tumours display a basal-like phenotype at the immunohistochemical and transcriptomic level, that epidermal growth factor receptor (EGFR) gene amplification is one of the underlying genetic mechanisms driving EGFR overexpression in these tumours, and that CAV1 (caveolin 1) and MRC2 (Endo180) are novel putative oncogenes amplified in metaplastic breast carcinomas.

Dr Reis-Filho has determined the molecular genetic characteristics of high grade breast cancers and confirmed that the majority of high grade breast cancers do not evolve from low grade cancers. His work, however, has also identified a group of high grade luminal cancers that harbour the hallmark genetic and immunophenotypical features of low grade breast cancers, suggesting that a subgroup of high grade oestrogen-receptor (ER) positive cancers may, indeed, originate from low grade tumours.

Using an integrative approach of high throughput molecular data, Dr Reis-Filho has identified novel therapeutic targets in the form of genes whose expression and activity are required for the survival of breast cancer cells harbouring their amplification, namely FGFR1 on 8p11.2, which is recurrently amplified and overexpressed in ~10% of ER positive breast cancers; PPM1D on 17q23.2, which is amplified and overexpressed in ~20% of HER2 amplified breast cancers; and FGFR2 on 10q26, which is amplified and overexpressed in ~5% of triple negative cancers. Inhibition of these genes either by RNA interference or chemical inhibitors was shown to be selectively lethal in tumour cells harbouring their amplification and clinical trials testing inhibitors of these genes are about to be initiated.

Apart from his research programme, Dr Reis-Filho also co-directs the Histopathology Core Facility at the Breakthrough Centre, and is directly involved in the implementation of high throughput molecular methods, and in the development of conditional mouse models and characterisation of the tumours these animals develop. In collaboration with Richard Marais’ group, Dr Reis-Filho has demonstrated that BRAF^V600E mutation is a founder event in melanomagenesis and that p16 loss of function is neither required nor sufficient for the development of the malignant phenotype in BRAF^V600E melanomas. Dr Reis-Filho has also contributed to the dissection of the transcriptional targets activated by BRAF mutations. The results of his work provide a molecular rationale for the use of BRAF inhibitors for the management of patients with melanomas harbouring BRAF activating mutations.