Towards personalised medicine for cancer

Towards personalised medicine for cancer From initial therapy to follow-up

Authors	R.J. Molenaar
Supervisors	C.J.F. van Noorden W.P. Vandertop
Cosupervisors	F.E. Bleeker J.W. Wilmink
Award date	22-12-2017
ISBN	9789462998124
Number of pages	260
Organisations	Faculty of Medicine (AMC-UvA)
Abstract	Overall, the studies described in the present dissertation are aimed at the improvement of personalised medicine strategies for various types of cancer. The studies in parts 1 and 2 describe potential novel therapeutic avenues to treat IDH1/2-mutated cancers and the conditions in which they may have optimal effects. The studies described in part 3 may improve risk/benefit assessments for the application of cytotoxic therapies in an individual patient, and the follow-up after the administration of such cytotoxic therapies. These nuances may ultimately improve personalized treatment and management of cancer.
Document type	PhD thesis
Language	English
Downloads	Thesis (complete) Front matter Chapter 1: General introduction Chapter 2: The driver and passenger effects of IDH1 and IDH2 mutations in oncogenesis, metabolic rewiring and survival prolongation Chapter 3: In silico gene expression analysis reveals glycolysis and acetate anaplerosis in IDH1 wildtype glioma and lactate and glutamate anaplerosis in IDH1-mutated glioma Chapter 4: Metabolic mapping: quantitative enzyme cytochemistry and histochemistry to determine the activity of dehydrogenases in cells and tissues Chapter 5: IDH1-mutated gliomas rely on glutamate to compensate for defective isocitrate processing: consequences for studies on IDH1 function Chapter 6: Tumour cells in search for glutamate: an alternative explanation for increased invasiveness of IDH1-mutated glioma Chapter 7: Targeting glutaminolysis in chondrosarcoma in context of the IDH1/2 mutation Chapter 8: Study protocol of a phase Ib/II clinical trial of metformin and chloroquine in patients with IDH1-mutated or IDH2-mutated solid tumours Chapter 9: The therapy-sensitizing effects of IDH1 and IDH2 mutations in cancer Chapter 10: Clinical and biological implications of ancestral and non-ancestral IDH1 and IDH2 mutations in myeloid neoplasms Chapter 11: The combination of IDH1 mutations and MGMT methylation status predicts survival in glioblastoma better than either IDH1 or MGMT alone Chapter 12: Robustness of IDH1/2 mutations, TERT mutations, and 1p/19q codeletions as prognostic tools in lower-grade glioma Chapter 13: Radioprotection of IDH1-mutated cancer cells by the IDH1-mutant inhibitor AGI-5198 Chapter 14: IDH1/2 mutations sensitise acute myeloid leukaemia to PARP inhibition and this is reversed by IDH1/2-mutant inhibitors Chapter 15: Myeloid neoplasia mutation rates differ in primary cases versus cases arising after cancers treated or not with radiation and/or chemotherapy Chapter 16: Haematopoietic stem cell niches, leukaemic cells and propagation of therapy-related myeloid neoplasms Chapter 17: Defining AML and MDS second cancer risk dynamics after diagnoses of first cancers treated or not with irradiation Chapter 18: Risk of haematologic malignancies following radioiodine treatment for welldifferentiated thyroid cancer Chapter 19: Risk of developing chronic myeloid neoplasms in well-differentiated thyroid cancer patients treated with radioactive iodine Chapter 20: Breast cancer tumour size and subsequent risks of acute myeloid leukaemia in patients treated with chemotherapy and radiotherapy Chapter 21: Risk of developing second haematological malignancies after irradiation and/or chemotherapy in adolescents and young adults Chapter 22: Absence of increased risks for glioma after contemporary radiation therapy for cancer in childhood and adolescents Chapter 23: Early and late risks of heart disease-related mortality after irradiation for oesophageal cancer: a population-based study among oesophageal cancer survivors Chapter 24: General discussion Chapter 25: Summary Chapter 26: Nederlandse samenvatting Appendices Stellingen
Supplementary materials	Electronic supplement
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Towards personalised medicine for cancer From initial therapy to follow-up