Research projects
Professor Udai Banerji, Clinical Pharmacology & Trials team
Phase I Trials at the Drug Development Unit
Phase I trials are conducted at the Drug Development Unit (DDU) of The Institute of Cancer Research and The Royal Marsden. The DDU runs phase I clinical trials of drugs discovered at, or in collaboration with, the ICR, such as pictilisib (PI3K inhibitor), luminespib (HSP90 inhibitor), CHR-3996 (HDAC inhibitor), AZD5363 (AKT inhibitor), ONX-0801 (alpha-folate-targeted TS inhibitor), AT13148 (AGC kinase inhibitor) and CCT3833 (panRAF inhibitor).
The unit runs trials sponsored by academic institutions and charities, such as Cancer Research UK, pharmaceutical companies, as well as investigator-initiated studies sponsored by the ICR and The Royal Marsden. The unit has 30-40 trials open at any given time and 250-300 patients a year enter phase I trials.
The DDU has close links with the Experimental Cancer Medicine Centres (ECMC) network and the National Institute for Health Research (NIHR) Biomedical Research Centres.
Current investigator-initiated phase I studies sponsored by the ICR/the Royal Marsden and led by Professor Banerji include: TAX-TORC (TORC1/2 inhibitor, AZD2014, in combination with weekly paclitaxel); ONX-0801 (alpha-folate targeted TS inhibitor); RO5126766 (RAF/MEK inhibitor).
Professor Banerji is part of the multidisciplinary team within the Division of Cancer Therapeutics which input into targets entering the drug discovery portfolio and reviews/advises on projects as they progress from discovery through to becoming clinical candidates.
Professor Banerji works closely with Professor Johann de Bono, who heads the Drug Development Unit, and with the Centre for Cancer Drug Discovery.
Pharmacodynamic biomarkers
Professor Banerji leads the Clinical Pharmacodynamic Biomarker Group. This group transfers assays used during drug discovery to platforms that can be used on human tissue sampled during phase I studies. Assays include: ELISA and immunofluorescence assays using platelet-rich plasma, peripheral blood mononuclear cells, hair follicles and tumour tissue.
The group validates and then uses these assays, which help define doses and schedules of novel anti-cancer agents. Examples of a wide range of assays include proof-of-mechanism biomarkers quantifying phosphoprotein levels, such as p-AKT, pGSK3ß, p-PRAS40, p-CHK1, p-IGFR and quantifying acetylated histone H3 and HSP70.
Drug resistance and combinations of targeted agents
Professor Banerji runs a translational research group, the Drug Evaluation and Pharmacodynamics Group, focusing on drug resistance and combinations of signal transduction inhibitors. The group has characterised PI3K signalling output in ovarian and lung cancer cells isolated from ascites and pleural effusions from patients with ovarian and lung cancer.
Findings from such studies led to hypothesis-testing studies, such as TAX-TORC, which associated elevated p-S6K levels with resistance to chemotherapy in ovarian cancer. The team has developed innovative multiplex phosphoprotein assays that simultaneously measure phosphoprotein levels in cell lines and patient tissue exposed to anti-cancer drugs ex vivo. Professor Banerji collaborates with Dr Bissan Al-Lazikani to model this data and translate these scientific findings to clinically actionable combinations.