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Investigation of prostate cancer stem cell targeting therapeutics with clinical potential


   Faculty of Life Sciences


About the Project

Prostate cancer (PCa) patients with aggressive disease are associated with <30% 5-year survival rates. This reflects the limited efficacy of current treatment options for metastatic castrate resistant prostate cancer (CRPC) (e.g. docetaxel), and highlights the unmet clinical need for new therapeutic strategies to prevent/treat CRPC. Previous work has demonstrated that aldehyde dehydrogenases (ALDHs) function to mediate cell differentiation and prostate cancer stem cell (PCSC) expansion and contribute to both chemo- and radiotherapy resistance. We have shown that targeting specific ALDH isoforms with small molecule inhibitors reduces PCa cell viability with potential to sensitise PCa cells to standard of care drugs. Emerging evidence indicates that hypoxic fractions play host to CSCs and this project seeks to explore how (i) hypoxia in the PCa microenvironment impacts on ALDH-expressing PCSC behaviour and (ii) ALDH-targeting inhibitors and prodrugs can be employed with existing therapies as a new treatment approach for aggressive PCa.  

Aim

To evaluate ALDH-targeting therapeutics as a new strategy to treat prostate cancer stem cells

Focus

Analysis of ALDH expression in drug-resistant PCa cell lines and PCSCs isolated from clinical samples. Evaluation of PCSC-targeting inhibitors and prodrugs in combination with standard of care drugs including androgen receptor antagonists or cytotoxic chemotherapy.

Who should apply

Applicants are expected to be fully committed to bench and clinical work, and ideally, also have knowledge/experience or interest in urological oncology. Candidates are expected to hold a Medical degree (MBChB, MBBS etc), completed pre-registration training, and hold or be eligible for full registration with the UK General Medical Council (GMC). An honorary clinical contract will be sought with the Bradford Teaching Hospitals NHS Foundation Trust at the appropriate level depending on the applicant’s experience. The successful applicant will participate in clinical activities and be supported to develop and maintain clinical competencies while whilst undergoing laboratory work for the PhD. The ratio of laboratory/clinical work will be agreed with laboratory and clinical supervisors.

We particularly encourage applications from the following under-represented groups as identified by the Office for Students:

  1. Black, Asian and Ethnic Minority students
  2. Disabled students 
  3. Female students
  4. Care leavers
  5. Polar Q1 and Q2 students
  6. Refugees (The University of Bradford is recognised as a University of Sanctuary)
  7. Estranged students
  8. Gypsy, Roma, Traveller students
  9. Children from military families, veterans and partners of military personnel.

Applications are invited from UK citizens. EU/International student applications are welcome, but will require additional funding; outstanding students may be eligible for a University bursary - please enquire.

Enquiries and how to apply:

You should submit a CV (max. 2 pages) and a covering letter/expression of interest outlining your background and interest in the project to principal supervisor Professor Klaus Pors (). Co-supervisors are ICT Director and Professor Sherif El-Khamisy and Consultant Urologist & Honorary Senior Clinical Lecturer Dr Chidi Molokwu.

Further information on our research and facilities can be found on our website.

Anticipated start date:

February 2023


Funding Notes

The studentship funded by the Masonic Charitable Foundation in partnership with the University of Bradford covers home tuition fees, a tax-free stipend (at standard MRC rates, currently £15,609 per annum 2021/22) for the duration programme and writing-up (3 years total) and a generous research budget. Funding for specific training courses is also included in the ICT DTC.

References

Ibrahim AIM et al., J Med Chem. 2022 Mar 10;65(5):3833-3848
Ibrahim AIM et al., Molecules. 2021 Sep 23;26(19):5770
Quattrini L et al., Biomedicines. 2020 Dec 4;8(12):E569
Ibrahim AIM et al., J Cancer Metastasis Treat 2018;4:1-17

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