Top
Skip to Content
LOGO(small) - Queen's University Belfast
  • Our twitter
  • Our facebook
  • Our
  • Our
LOGO(large) - Queen's University Belfast

The Patrick G Johnston Centre for Cancer Research

  • Home
  • Our Science
    • Tumour Specialisms and Clinical Trials
    • Disciplinary Strengths
    • Technology Specialisms
    • Major Research Programmes
  • Education
    • Clinical Academic Training
    • Postgraduate Research
    • Postgraduate Taught
    • Princess Margaret Cancer Centre
    • Summer Research Programme
    • Undergraduate
  • Impact
    • Videos
    • Seminars and Events
    • Research Engagement
    • Industry and Innovations
    • Bulletins and Annual Reports
  • Cancer Digest
    • Blood Cancer
    • Breast Cancer
    • Digital Pathology
    • Prostate Cancer
    • Radiotherapy
    • Bowel Cancer
  • Opportunities
    • Academic Posts
    • Postdoctoral
    • PhD Opportunities
  • Contact Us
    • Academic Staff
    • Administrative Staff
    • Clinical Academic Training Programme
    • Clinical Research Fellows
    • Honorary Staff
    • Research Staff
    • Technical Staff
  • News
  • Donate
  • Home
  • Our Science
    • Tumour Specialisms and Clinical Trials
    • Disciplinary Strengths
    • Technology Specialisms
    • Major Research Programmes
  • Education
    • Clinical Academic Training
    • Postgraduate Research
    • Postgraduate Taught
    • Princess Margaret Cancer Centre
    • Summer Research Programme
    • Undergraduate
  • Impact
    • Videos
    • Seminars and Events
    • Research Engagement
    • Industry and Innovations
    • Bulletins and Annual Reports
  • Cancer Digest
    • Blood Cancer
    • Breast Cancer
    • Digital Pathology
    • Prostate Cancer
    • Radiotherapy
    • Bowel Cancer
  • Opportunities
    • Academic Posts
    • Postdoctoral
    • PhD Opportunities
  • Contact Us
    • Academic Staff
    • Administrative Staff
    • Clinical Academic Training Programme
    • Clinical Research Fellows
    • Honorary Staff
    • Research Staff
    • Technical Staff
  • News
  • Donate
  • Our twitter
  • Our facebook
  • Our
In This Section
  • Therapy Resistance
  • DNA Damage Signalling
  • Tumour Microenvironment Biology
  • Tumour Epidemiology and Early Detection

  • Home
  • The Patrick G Johnston Centre for Cancer Research
  • Our Science
  • Disciplinary Strengths
  • Therapy Resistance

Therapy Resistance

Pharmacy Research Banner 1600 X 575
Disciplinary strengths
Therapy Resistance

Resistance to all anti-cancer therapies is a major problem. Mechanisms of resistance frequently involve activation of survival pathways, ineffective induction of cell death, defective DNA damage repair pathways, epigenetic reprogramming, altered metabolism and ineffective tumour recognition and elimination by the immune system.

In the PGJCCR, we undertake pre-clinical research into all of the above mechanisms as well as research using clinical samples to identify patients with drug-resistant cancers who will most likely not benefit from current treatments (patient stratification).

Patient Stratification (personalizing cancer treatment)

Colorectal cancer (CRC) is the second most common cause of cancer death in the UK equating to more than 16,000 deaths from the disease each year. In order to treat this disease more effectively we must first understand the molecular drivers causing drug resistance and/or disease relapse. Advances in molecular analysis in the past 10 years have markedly improved our biological understanding of CRC, and research from the PGJCCR in the area of molecular stratification is beginning to inform standard patient care. 

Dysfunctional Cell Death

Programmed cell death (called “apoptosis”) is important for maintaining homeostatic balance in our organs. About 50,000,000,000 cells die each day (nearly a million per second!) in the average human adult and these are replaced by new cells. In cancer the balance goes wrong – cancer cells become resistant to apoptosis; this is one of their hallmarks.  With chemotherapy, radiotherapy and other types of cancer therapy, the goal is to kill the cancer cells, but if they are resistant to apoptosis, this can make them resistant. 

Researchers in PGJCCR perform research into the fundamental mechanisms of cell death in order to understand how these go wrong at a molecular level in cancer cells. The goal is to use this understanding to develop new treatments that overcome drug resistance by reactivating the faulty cell death mechanisms present in cancer cells

Pro-survival Signaling

Tumours are highly adaptable, and the activation of pro-survival pathways during drug treatment and consequent inactivation of downstream death signalling pathways can also contribute to drug resistance. Current research efforts in PGJCCR focus on identifying and targeting both acute and acquired pro-survival signalling following both standard-of-care chemotherapy and molecularly targeted therapies, in particular within the context of oncogene-driven tumours (eg. oncogenic RAS and BRAF CRC, oncogenic EGFR NSCLC). 

A number of ongoing studies are focusing on the role of ADAMs (a desintegrin and metalloprotease), in particular ADAM17, in regulating receptor tyrosine kinase and resistance to chemotherapy and targeted therapies. Other studies aim to identify and target oncogenic bypass mechanism following treatment with targeted therapies, such as inhibition of BRAF/MEK, KRAS and EGFR in BRAF mutated, KRAS mutated and KRAS wild type colorectal cancer tumours respectively and EGFR in mutant EGFR driven NSCLC.

Epigenetics and transcription

Changes in gene transcription in response to treatment underpinned by epigenetic plasticity play a crucial role in determining not only the initial response to treatment, but also drug tolerance, enabling emergence of resistance.  A number of groups in the PGJCCR are focused on understanding and exploiting the transcriptional and epigenetic changes that occur in cancer.

The use of cutting edge functional genomics technologies and integrative bioinformatics strategies is increasingly allowing us to identify novel disease specific dependencies linked to the genetic changes that occur in specific cancer sub-types, which can be exploited for diagnostic or therapeutic application.

Metabolic Reprogramming: opportunities for therapeutic intervention

Cancer cells frequently hijack the metabolic processes hardwired in normal cells to support their enhanced growth, proliferation and spread. Importantly, changes in tumour cell metabolism can present novel vulnerabilities, that when targeted pharmacologically can limit tumour growth; and also alter the sensitivity of these tumour cells to standard-of-care chemotherapies and targeted therapies. Thus, defining the impact of metabolic reprogramming on dictating therapeutic susceptibilities and driving resistance mechanisms is imperative to improving treatment response for cancer patients.

Our aim is to integrate state-of-the-art cancer models, metabolic analyses and multi-omics platforms to comprehensively map metabolic reprogramming, uncover induced vulnerabilities, mechanisms of drug resistance and novel therapeutic opportunities in defined cancer subtypes (KRASmutant, TP53mutant/null, APCmutant/null), allowing us to better aid in patient stratification, and suggesting novel therapeutic combinations to improve patient outcome.

Principal Investigator Links

Prof Dan Longley Dr Emma Kerr
Dr Simon McDade Dr Sandra Van Schaeybroeck
Dr Philip Dunne Dr Kienan Savage
Dr Paul Mullan Dr Ian Overton
Prof Tim Harrison Prof Chris Scott
Prof Ian Mills

Medical research student working from behind a protective screen

Disciplinary Strengths
  • Disciplinary Strengths
  • Therapy Resistance
  • DNA Damage Signalling
  • Tumour Microenvironment Biology
  • Tumour Epidemiology and Early Detection
Queen's University Belfast - Logo (small)
Contact Us

The Patrick G Johnston Centre for Cancer Research

Queen's University Belfast
97 Lisburn Road
Belfast
BT9 7AE

Phone: +44 (0) 28 9097 2760
Email: pgjccr@qub.ac.uk  
Fax: +44 (0) 28 9097 2776

Quick Links

  • Home
  • Our Science
  • Education

 

© Queen's University Belfast 2023
Privacy and cookies
Website accessibility
Freedom of information
Modern slavery statement
Equality, Diversity and Inclusion
Manage cookies