Dónal Landers

Dónal Landers
Cancer Research UK Manchester Institute · digital Experimental Cancer Medicine Team

MB BCh BAO, MBA, DPM, FFPM, PGCert (Trans Med)

About

51
Publications
5,309
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692
Citations
Introduction
Dónal Landers is Strategic Director of the digital Experimental Cancer Medicine Team (digital ECMT) part of Cancer Biomarker Centre (CBC) team based at the Cancer Research UK Manchester Institute. Dónal conducts research in Oncology and Decision Science - please see http://www.digitalecmt.org for further information.
Additional affiliations
January 2021 - present
Cancer Research UK Manchester Institute
Position
  • Managing Director
Description
  • Th digital ECMT 2021-2025 vision is to digitally empower patients and healthcare professionals to innovate and design new cancer care pathways. Our Mission is to provide next generation patient cancer care through comprehensive data-driven evidence to enable: 1. The transformation of clinical decision-making; 2. Evolve the role of the patient and; 3. Improve patient outcomes. We actively support collaborative research - contact us at donal.landers@digitalecmt.org
February 2019 - present
DeLondra Oncology Ltd.
Position
  • Managing Director
Description
  • Provision of Pharmaceutical Medicine consultancy to Pharma in early oncology drug development: - Strategy development - Clinical and Translational Science program development - Clinical Platform Trial Design and Development - Clinical Trial analytics
January 2018 - present
The University of Manchester
Position
  • Lecturer
Description
  • Masters in Research (MRes) Programme
Education
September 1983 - June 2021
Trinity College Dublin
Field of study
  • Medicine

Publications

Publications (51)
Article
Full-text available
Background Molecular Tumour Boards (MTBs) were created with the purpose of supporting clinical decision-making within precision medicine. Though in use globally, reporting on these meetings often focuses on the small percentages of patients that receive treatment via this process and are less likely to report on, and assess, patients who do not rec...
Preprint
Full-text available
Entailment trees have been proposed to simulate the human reasoning process of explanation generation in the context of open--domain textual question answering. However, in practice, manually constructing these explanation trees proves a laborious process that requires active human involvement. Given the complexity of capturing the line of reasonin...
Preprint
In this paper we provide a structured literature analysis focused on Deep Learning (DL) models used to support inference in cancer biology with a particular emphasis on multi-omics analysis. The work focuses on how existing models address the need for better dialogue with prior knowledge, biological plausibility and interpretability, fundamental pr...
Preprint
Full-text available
Cytokine release syndrome (CRS), also known as cytokine storm, is one of the most consequential adverse effects of chimeric antigen receptor therapies that have shown promising results in cancer treatment. When emerging, CRS could be identified by the analysis of specific cytokine and chemokine profiles that tend to exhibit similarities across pati...
Article
Full-text available
We conducted a phase IIa, multi-centre, open label, single arm study (RADICAL; NCT01791985) of AZD4547 (a potent and selective inhibitor of Fibroblast Growth Factor Receptor (FGFR)-1, 2 and 3 receptor tyrosine kinases) administered with anastrozole or letrozole in estrogen receptor positive metastatic breast cancer patients who had become resistant...
Article
PURPOSE Patients with cancer are at increased risk of severe COVID-19 disease, but have heterogeneous presentations and outcomes. Decision-making tools for hospital admission, severity prediction, and increased monitoring for early intervention are critical. We sought to identify features of COVID-19 disease in patients with cancer predicting sever...
Preprint
Full-text available
This paper contributes with a pragmatic evaluation framework for explainable Machine Learning (ML) models for clinical decision support. The study revealed a more nuanced role for ML explanation models, when these are pragmatically embedded in the clinical context. Despite the general positive attitude of healthcare professionals (HCPs) towards exp...
Article
Full-text available
Objectives COVID-19 is a heterogeneous disease, and many reports have described variations in demographic, biochemical and clinical features at presentation influencing overall hospital mortality. However, there is little information regarding longitudinal changes in laboratory prognostic variables in relation to disease progression in hospitalised...
Preprint
Full-text available
BioBERT and BioMegatron are Transformers models adapted for the biomedical domain based on publicly available biomedical corpora. As such, they have the potential to encode large-scale biological knowledge. We investigate the encoding and representation of biological knowledge in these models, and its potential utility to support inference in cance...
Article
Full-text available
Objectives Dexamethasone has now been incorporated into the standard of care for COVID-19 hospital patients. However, larger intensive care unit studies have failed to show discernible improvements in mortality in the most recent wave. We aimed to investigate the impacts of these factors on disease outcomes in a UK hospital study. Methods This retr...
Conference Paper
Full-text available
SemEval is the primary venue in the NLP community for the proposal of new challenges and for the systematic empirical evaluation of NLP systems. This paper provides a systematic quantitative analysis of SemEval aiming to evidence the patterns of the contributions behind SemEval. By understanding the distribution of task types, metrics, architecture...
Preprint
Full-text available
Molecular Tumour Boards (MTBs) were created with the purpose of supporting clinical decision making within precision medicine. Though these meetings are in use globally reporting often focuses on the small percentages of patients that receive treatment via this process and are less likely to report on, and assess, patients who do not receive treatm...
Preprint
Full-text available
This paper proposes a novel statistical corpus analysis framework targeted towards the interpretation of Natural Language Processing (NLP) architectural patterns at scale. The proposed approach combines saturation-based lexicon construction, statistical corpus analysis methods and graph collocations to induce a synthesis representation of NLP archi...
Preprint
Full-text available
This paper describes N-XKT (Neural encoding based on eXplanatory Knowledge Transfer), a novel method for the automatic transfer of explanatory knowledge through neural encoding mechanisms. We demonstrate that N-XKT is able to improve accuracy and generalization on science Question Answering (QA). Specifically, by leveraging facts from background ex...
Article
Full-text available
Durvalumab is a programmed death-ligand 1 (PD-L1) inhibitor with clinical activity in advanced urothelial cancer (AUC)¹. AUC is characterized by several recurrent targetable genomic alterations2–5. This study (NCT02546661, BISCAY) combined durvalumab with relevant targeted therapies in biomarker-selected chemotherapy-refractory AUC populations incl...
Article
Full-text available
Health care needs to continuously evolve and innovate to maintain the health of populations. Technology has the potential to enable better patient engagement and ownership, as well as optimise therapeutic interventions and data-science approaches to facilitate improved health care decisions. Yet, to date, technological innovation has not resulted i...
Article
Full-text available
Introduction The COVID-19 pandemic caused by SARS-CoV-2 places immense worldwide demand on healthcare services. Earlier identification of patients at risk of severe disease may allow intervention with experimental targeted treatments, mitigating the course of their disease and reducing critical care service demand. Methods and analysis This prospe...
Conference Paper
Background: DNA-dependent protein kinase (DNA-PK) is a critical sensor of DNA double-strand breaks (DSBs) and orchestrates their repair through non-homologous end joining (NHEJ). AZD7648 is a novel, potent and highly selective inhibitor of DNA-PK being evaluated as monotherapy or in combination with doxorubicin or olaparib in a Phase I/II first-in-...
Article
Full-text available
Background Durvalumab (D), a PD-L1 inhibitor with efficacy in platinum refractory advanced urothelial cancer (UC), was investigated by combining with targeted therapy inhibitors (FGFR1,2,3, PARP, TORC 1 + 2) with a PD-L1 monotherapy arm (D alone) as a non-randomized control. An FGFRi monotherapy arm was also included. Methods Platinum refractory,...
Article
4553 Background: BISCAY is a biomarker-directed Ph1b multi-arm platform study exploring the combination of targeted therapies with anti-PD-L1, Durvalumab, in advanced urothelial cancer. Methods: Next generation sequencing (NGS) of tumour tissue samples from > 380 patients(pts) was performed using the FoundationOne assay alongside IHC for PD-L1. ct...
Article
Full-text available
Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) supports blood-based genomic profiling but is not yet routinely implemented in the setting of a phase I trials clinic. TARGET is a molecular profiling program with the primary aim to match patients with a broad range of advanced cancers to early phase clinical trials on the basis of...
Conference Paper
Full-text available
Introduction Breast cancer is the most common invasive cancer among women. Currently, there are only a few models used for therapy selection, and they are often poor predictors of therapeutic response or take months to set up and assay. In this report, we introduce a microfluidic OrganoPlate platform for extracellular matrix (ECM) embedded tumour c...
Conference Paper
Full-text available
Background: Patients with metastatic ER+ breast cancer almost invariably experience disease progression whilst taking AIs. Fibrob-last growth factor receptor inhibitors, e.g. AZD4547, can reverse endocrine resistance in breast cancer cells. Consequently, we designed the RADICAL trial to test safety and efficacy of AZD4547 combined with letrozole (L...
Article
Full-text available
Background AZD4547 is a potent, oral, highly selective fibroblast growth factor receptor (FGFR) inhibitor in clinical development for treating tumours with a range of FGFR aberrations, including FGFR mutations, amplifications and fusions. Methods This open-label, Phase I, multicentre study (NCT01213160) evaluated the safety, pharmacokinetics, and p...
Article
Full-text available
Purpose: Squamous cell lung cancers (SQCLC) account for 25% of all NSCLCs, yet the prognosis of these patients is poor and treatment options are limited. Amplified FGFR1 is one of the most common oncogenic events in SQCLCs, occurring in ~20% of cases. AZD4547 is a potent and selective FGFR1-3 inhibitor with anti-tumor activity in FGFR1 amplified S...
Conference Paper
Background: Patients with metastatic ER positive breast cancer invariably experience disease progression whilst taking AIs. Fibroblast growth factor receptor inhibitors (FGFRI) such as AZD4547 can reverse endocrine resistance in breast cancer cells. Consequently, we designed the RADICAL trial to test the safety and efficacy of AZD4547 combined with...
Article
Full-text available
Background: Approximately 5%–10% of gastric cancers have a fibroblast growth factor receptor-2 (FGFR2) gene amplification. AZD4547 is a selective FGFR-1, 2, 3 tyrosine kinase inhibitor with potent preclinical activity in FGFR2 amplified gastric adenocarcinoma SNU16 and SGC083 xenograft models. The randomized phase II SHINE study (NCT01457846) inves...
Article
1059 Background: Patients with metastatic ER positive breast cancer invariably experience disease progression whilst taking AIs. Fibroblast growth factor receptor inhibitors (FGFRI) such as AZD4547 can reverse endocrine resistance in breast cancer cells. Consequently, we designed the RADICAL trial to test the safety and efficacy of AZD4547 combined...
Poster
Background: gemcitabine (G) plus cisplatin (C) is a standard-of-care, combination chemotherapy regimen for patients (pts) with bladder cancer (BC), in both neoadjuvant and palliative settings. AZD4547 is a selective fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor with potential to improve outcomes for tumors with FGFR mutation an...
Conference Paper
Background: Despite progress with immunotherapy (IO), there remains a significant unmet medical need for patients with metastatic urothelial bladder cancer (UBC). A patient’s molecular tumour profile enables a targeted small molecule (SM) + IO approach to treatment, particularly in PD-L1 -ve patients. Tumour biomarker profiling to enrol for trials...
Article
Full-text available
Introduction: During early clinical testing of a new medication, it is critical to understand and characterise patient tolerability. However, in early clinical studies, it is difficult for patients to contribute directly to the sponsors' understanding of a new compound. Patient reported opinions about clinical tolerability (PROACT) provides a new,...
Article
Full-text available
Background: Urothelial cancers (UC) are the fourth most common tumours worldwide after prostate (or breast), lung and colorectal cancer. Despite recent improvements in their management, UC remain an aggressive disease associated with a poor outcome. Following disease progression on first-line platinum-based chemotherapy, very few effective treatme...
Poster
Full-text available
We have developed PROACT (Patient Reported Opinions About Clinical Tolerability), a mobile application designed to empower patients participating in early clinical studies. • It is a unique, patient-centric approach to engaging and working with patients as partners in a clinical study. • PROACT allows the patient to create a portable ‘video diary’...
Conference Paper
Full-text available
Yung-Jue Bang, Eric Van Cutsem, Was Mansoor, Russel Petty, Yee Chao, David Cunningham, David Ferry, Dónal Landers,Paul Stockman, Neil Smith, Catherine Geh, Elaine Kilgour
Conference Paper
Background Patients with metastatic breast cancer invariably experience disease progression whilst taking non-steroidal aromatase inhibitors (NSAIs). Fibroblast growth factor receptor inhibitors (FGFRI) can reverse endocrine resistance in breast cancer cells in vitro. Consequently, the RADICAL trial tested whether the FGFRI AZD4547 can be safely c...
Article
Full-text available
Aim: Fibroblast growth factors (FGFs) and their receptors (FGFRs) control a wide range of biological functions, and are implicated in the pathogenesis of diverse tumour types including gastro-oesophageal adenocarcinoma (OGA). AZD4547 is a potent, selective, small molecule inhibitor of FGFR 1, 2, & 3 tyrosine kinases. The aims of the phase I compone...
Conference Paper
Full-text available
Aim To use visualization technologies to inform early Go/No-Go (GNG) decisions in clinical development. Methods The project engaged experts (DM, programming, statistics, informatics, clinical operations, physicians) to develop an innovative internal solution. TIBCO Spotfire [1] was used to design near real-time visualisations for safety [2], toler...
Article
531 Background: Preclinical data suggest a key role for EGFR inhibition in delaying acquired resistance to ET in ER+ breast cancer (BC). Retrospective analyses of 2 Phase II studies suggested adding gefitinib to ET delayed PFS in ET naive (ETN) BC. This randomized, double-blind, placebo-controlled multi-center study (NCT01151215) was conducted to p...
Article
Background: AZD8931 is an oral, equipotent inhibitor of EGFR, HER2, and HER3 signaling. Preclinical evidence indicates that AZD8931 may be particularly potent when HER signaling is ligand driven, which is thought to be the signaling mechanism that is more prevalent in low HER2-expressing BC. Methods: In this double-blind multicenter phase II study,...
Article
Background: Preclinical data suggest a key role for EGFR inhibition in delaying acquired resistance to ET in ER+ breast cancer (BC). Retrospective analyses of 2 Phase II studies suggested adding gefitinib to ET delayed PFS in ET naive (ETN) BC. This randomized, double-blind, placebo-controlled multi-center study (NCT01151215) was conducted to prosp...
Article
Full-text available
Most federations of healthcare systems have operated in an in-house environment where local area networks coupled with layers of interoperability were used to connect various information systems. More recently, a need has arisen to connect large institutions such as hospitals, with wider area applications such as general practice systems in order t...

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