Treatment Strategies for Primarily Generalized Colorectal Cancer
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer,Colorectal Neoplasms
PROVIDER: 2084023 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:<p>Neoantigens, which are derived from tumour-specific protein-coding mutations, are exempt from central tolerance, can generate robust immune responses and can function as bona fide antigens that facilitate tumour rejection. We demonstrated that a strategy that uses multi-epitope, personalized neoantigen vaccination, which has previously been tested in patients with high-risk melanoma, is feasible for tumours such as glioblastoma, which typically have a relatively low mutation load and an immunologically ‘cold’ tumour microenvironment. Here we conducted whole-exome sequencing of tumor and normal cells from individual patients with glioblastoma to identify tumor-specific mutations. We assessed the expression of mutated alleles by RNA-sequencing of tumor. We used personalized neoantigen-targeting vaccines to immunize patients newly diagnosed with glioblastoma following surgical resection and conventional radiotherapy in a phase I/Ib study. Patients who did not receive dexamethasone-a highly potent corticosteroid that is frequently prescribed to treat cerebral oedema in patients with glioblastoma-generated circulating polyfunctional neoantigen-specific CD4+ and CD8+ T cell responses that were enriched in a memory phenotype and showed an increase in the number of tumour-infiltrating T cells. Using single-cell T cell receptor analysis, we provide evidence that neoantigen-specific T cells from the peripheral blood can migrate into an intracranial glioblastoma tumour. Neoantigen-targeting vaccines thus have the potential to favourably alter the immune milieu of glioblastoma.</p>
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Project description:The paper describes a model of resistance of cancer to chemotherapy.
Created by COPASI 4.25 (Build 207)
This model is described in the article:
Modelling chemotherapy resistance in palliation and failed cure
Helen C. Monro, Eamonn A. Gaffney
J Theor Biol. 2009, 257 (2), pp.292
Abstract:
The goal of palliative cancer chemotherapy treatment is to prolong survival and improve quality of life when tumour eradication is not feasible. Chemotherapy protocol design is considered in this context using a simple, robust, model of advanced tumour growth with Gompertzian dynamics, taking into account the effects of drug resistance. It is predicted that reduced chemotherapy protocols can readily lead to improved survival times due to the effects of competition between resistant and sensitive tumour cells. Very early palliation is also predicted to quickly yield near total tumour resistance and thus decrease survival duration. Finally, our simulations indicate that failed curative attempts using dose densification, a common protocol escalation strategy, can reduce survival times.
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