The role of biological and chronological age in cancer treatment

1 PhD project offered in the IPP summer call 2021

This project is part of the Science of Healthy Ageing Research Programme (SHARP).

Scientific background

Glioblastoma is the most common primary malignant brain tumor in adults over 70 years of age with a dismal prognosis. In light of frequent comorbidities, and an increased risk of toxic effects from chemo- and radiation therapy on the ageing brain, glioblastoma management in patients 65 years of age or older is exceedingly complex and treatment decisions are frequently based on chronological age. A growing body of evidence indicates that the biological age and the extent of ‘frailty’ are far more informative predictors of treatment tolerance, outcome and overall survival than chronological age. To date, very few studies have used molecular biomarkers of frailty to assess the response to treatment, let alone guide treatment decisions. Similarly, longitudinal studies of frailty markers are urgently needed and hold tremendous promise for improving treatment outcomes through personalized treatment plans. In a translational study aimed at the development of a prediction tool for individualized glioblastoma therapy, we will correlate treatment responses with a questionnaire-based frailty index and a set of molecular characteristics derived from patient samples prior to and over the course of treatment. By combining clinical expertise in geriatrics and neurosurgery with molecular- and cell-biological analysis and bioinformatics we will develop tools to better predict treatment outcomes for elderly patients with glioblastoma. The development of such prediction tools will mark an important step towards individualized treatment approaches in a rapidly ageing society.

PhD project: “Defining molecular markers of frailty in the context of glioblastoma diagnosis and treatment”

The aim of this PhD project is to define molecular markers of frailty to best assess the biological age of patients, document responses to treatment at the molecular level and aid in future treatment decisions. The project is anchored in a highly interdisciplinary environment between molecular biology, neurosurgery and geriatrics and is based on various research techniques including primary cell culture, telomere and epigenetic analyses, histology and microscopy, next-generation sequencing and bioinformatics, as well as various functional assays to assess responses to chemotherapy ex vivo. We are therefore looking for a highly motivated PhD candidate with good communication skills, wet lab experience and the ability to drive the project.

If you are interested in this project, please select Peter Baumann (in collaboration with Beat Alessandri) as your group preference in the IPP application platform.

Publications relevant to this project

Kane AE, Sinclair DA (2019) Frailty biomarkers in humans and rodents: Current approaches and future advances. Mech Ageing Dev, 180:117-128 Link

Renovanz M, Hickmann AK, Nadji-Ohl M, Keric N, Weimann E, Wirtz CR, Singer S, Ringel F, Coburger J (2020) Health-related quality of life and distress in elderly vs. younger patients with high-grade glioma-results of a multicenter study. Support Care Cancer, 28(11):5165-5175 Link

Krenzlin H, Gresser E, Jussen D, Riede N, Taylor L, Vogelaar CF, Ringel F, Kempski O, Alessandri B (2020) The Cerebral Thrombin System Is Activated after Intracerebral Hemorrhage and Contributes to Secondary Lesion Growth and Poor Neurological Outcome in C57Bl/6 Mice. J Neurotrauma, 37(12):1481-1490 Link

Krenzlin H, Frenz C, Schmitt J, Masomi-Bornwasser J, Wesp D, Kalasauskas D, Kerz T, Lotz J, Alessandri B, Ringel F, Keric N (2020) High CSF thrombin concentration and activity is associated with an unfavorable outcome in patients with intracerebral hemorrhage. PLoS One, 15(11):e0241565 Link

Tseng CK, Wang HF, Schroeder MR, Baumann P (2018) The H/ACA complex disrupts triplex in hTR precursor to permit processing by RRP6 and PARN.Nat Commun, 9(1):5430 Link

 

Contact

Prof. Peter Baumann (If you are interested in this project, please select Peter Baumann (in collaboration with Beat Alessandri) as your group preference in the IPP application platform.)

Email

Webpage

Dr Beat Alessandri

Email

Webpage