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Addressing the problem of postoperative cancer relapses

  • Full or part time
  • Application Deadline
    Friday, March 13, 2020
  • Competition Funded PhD Project (Students Worldwide)
    Competition Funded PhD Project (Students Worldwide)

Project Description

Using computer simulation and access to databases for patients treated with surgery, it was
proposed that relapses within 3 years of surgery are stimulated by the surgical procedure.
In vitro and in vivo experiments have suggested plausible mechanisms, but the problem remains largely under investigated. Several studies indicate that inflammatory pathways are implicated in postoperative cancer recurrences (1,2). Since nearly all anaesthetic and analgesic drugs affect anticancer immunity and other tumour-promoting pathways (such as angiogenesis and VEGF), a huge potential exists for drugs and techniques repurposing (3,4).

But the bimodality in the relapse frequency over time after cancer surgery has recently been challenged (5). An early peak, occurring in the first 18 postoperative months, has been observed previously in breast cancer patients but seemed less clear, if any, in most recent data. Risk factors for the occurrence of the early peak should then be investigated, using epidemiological approach and in large databases. The analysis of the evolution of the landscape of postoperative cancer relapses during the last twenty years may explain discrepancies in the literature, and open great opportunities.

This approach may help to design new works that are needed to investigate the patients’ subgroups that may specifically benefit from intraoperative interventions during cancer surgery. These works may focus on the identification of relevant biomarkers, and their evolution after surgery.

Ultimately, the work may include an ambitious participation to the building of a multicancer-trials platform aiming to combine oncological surgical/medical treatment with the most promising techniques and molecules, recently suggested by a European consortium of researchers working in the field. The suggested techniques included: interventions on angiogenesis, neuromodulation, immunomodulation, nutrition, pre-habilitation; suggested molecules: amide-type local anaesthetics, non-steroidal anti-inflammatory drugs, opioids vs. opioid-sparing/free strategies, volatile vs. inhaled anaesthesia, beta-blockers)(6).

APPLICATION PROCEDURE:
This project is advertised in relation to the research areas of APPLIED HEALTH SCIENCE. Formal applications can be completed online: https://www.abdn.ac.uk/pgap/login.php. You should apply for Degree of Doctor of Philosophy in Applied Health Science, to ensure that your application is passed to the correct person for processing.

NOTE CLEARLY THE NAME OF THE SUPERVISOR AND EXACT PROJECT TITLE ON THE APPLICATION FORM. Applicants are limited to applying for a maximum of 3 applications for funded projects. Any further applications received will be automatically withdrawn.

Funding Notes

This project is funded by a University of Aberdeen Elphinstone Scholarship. An Elphinstone Scholarship covers the cost of tuition fees only, whether home, EU or overseas.

For details of fees: View Website

Candidates should have (or expect to achieve) a minimum of a First Class Honours degree in a relevant subject. Applicants with a minimum of a 2:1 Honours degree may be considered provided they have a Distinction at Masters level.

References

(1) Hiller JG, Perry NJ, Poulogiannis G, Riedel B, Sloan EK. Perioperative events influence cancer recurrence risk after surgery. Nat Rev Clin Oncol. 2018;15(4):205-218

(2) Krall JA, Reinhardt F, Mercury OA, Pattabiraman DR, Brooks MW, Dougan M, Lambert AW, Bierie B, Ploegh HL, Dougan SK, Weinberg RA.The systemic response to surgery triggers the outgrowth of distant immune-controlled tumors in mouse models of dormancy. Sci Transl Med. 2018;10(436).

(3) Forget P, Collet V, Lavand'homme P, De Kock M. Does analgesia and condition influence immunity after surgery? Effects of fentanyl, ketamine and clonidine on natural killer activity at different ages. Eur J Anaesthesiol. 2010;27(3):233-40.

(4) Shakhar G, Ben-Eliyahu S. Potential prophylactic measures against postoperative immunosuppression: Could they reduce recurrence rates in oncological patients? Ann Surg Oncol 2003;10(8):972-92.

(5) Forget P, Bouche G, Duhoux FP, Coulie PG, Decloedt J, Dekleermaker A, Guillaume JE, Ledent M, Machiels JP, Mustin V, Swinnen W, van Maanen A, Vander Essen L, Verougstraete JC, De Kock M, Berliere M. Intraoperative ketorolac in high-risk breast cancer patients. A prospective, randomized, placebo-controlled clinical trial. PLoS One. 2019 Dec 4;14(12):e0225748.

(6) Forget P, Aguirre JA, Bencic I, Borgeat A, Cama A, Condron C, Eintrei C, Eroles P, Gupta A, Hales TG, Ionescu D, Johnson M, Kabata P, Kirac I, Ma D, Mokini Z, Guerrero Orriach JL, Retsky M, Sandrucci S, Siekmann W, Štefančić L, Votta-Vellis G, Connolly C, Buggy D. How Anesthetic, Analgesic and Other Non-Surgical Techniques During Cancer Surgery Might Affect Postoperative Oncologic Outcomes: A Summary of Current State of Evidence. Cancers (Basel). 2019 Apr 28;11(5).

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