Journal Article

Gemcitabine potentiates the anti-tumour effect of radiation on medullary thyroid cancer

Montelius, Mikael, Ståhl, Ingun, Shubbar, Emman, Nilsson, Ola, Sandblom, Viktor, Spetz, Johan, Swanpalmer, John, Forssell-Aronsson, Eva

2019

Overview

Patients with medullary thyroid cancer (MTC) are often diagnosed with spread tumour disease and the development of better systemic treatment options for these patients is important. Treatment with the radiolabelled somatostatin analogue 177Lu-octreotate is already a promising option but can be optimised. For example, combination treatment with another substance could increase the effect on tumour tissue. Gemcitabine is a nucleoside analogue that has been shown to sensitise tumour cells to radiation. The aim of this study was to investigate potentially additive or synergistic effects of combining radiation with gemcitabine for treatment of MTC. Nude mice transplanted with patient-derived MTC tumours (GOT2) were divided into groups and treated with radiation and/or gemcitabine. Radiation treatment was given as 177Lu-octreotate or external beam radiotherapy (EBRT). The volume of treated and untreated tumours was followed. The absorbed dose and amount of gemcitabine were chosen to give moderate tumour volume reduction when given as monotherapy to enable detection of increased effects from combination treatment. After follow-up, the mice were killed and tumours were immunohistochemically (IHC) analysed. Overall, the animals that received a combination of EBRT and gemcitabine showed the largest reduction in tumour volume. Monotherapy with EBRT or gemcitabine also resulted in a clear detrimental effect on tumour volume, while the animals that received 177Lu-octreotate monotherapy showed similar response as the untreated animals. The GOT2 tumour was confirmed in the IHC analyses by markers for MTC. The IHC analyses also revealed that the proliferative activity of tumour cells was similar in all tumours, but indicated that fibrotic tissue was more common after EBRT and/or gemcitabine treatment. The results indicate that an additive, or even synergistic, effect may be achieved by combining radiation with gemcitabine for treatment of MTC. Future studies should be performed to evaluate the full potential of combining 177Lu-octreotate with gemcitabine in patients.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Analogue / Animals / Anticancer properties / Antineoplastic agents / Biology and Life Sciences / Biomedical engineering / Cancer / Cancer and Oncology / Cancer och onkologi / Cancer patients / Cancer therapies / Cancer treatment / Carcinoma, Neuroendocrine - diagnosis / Carcinoma, Neuroendocrine - metabolism / Carcinoma, Neuroendocrine - therapy / Cell cycle / Cytotoxicity / Deoxycytidine - analogs & derivatives / Deoxycytidine - pharmacology / Deoxycytidine - therapeutic use / Deoxyribonucleic acid / Development and progression / DNA / Dosage / Fibrosis / Future predictions / Gemcitabine / Health aspects / Health physics / Hospitals / Humans / Immunohistochemistry / Lutetium isotopes / Medical research / Medical treatment / Medicine and Health Sciences / Metabolites / Metastasis / Mice / Neuroendocrine tumors / Nuclear medicine / Nucleoside analogs / Nucleosides / Octreotide - analogs & derivatives / Octreotide - pharmacology / Octreotide - therapeutic use / Patients / Peptides / Physics / Radiation / Radiation (Physics) / Radiation effects / Radiation therapy / Radiation-Sensitizing Agents - pharmacology / Radiation-Sensitizing Agents - therapeutic use / Radiologi och bildbehandling / Radiology and Medical Imaging / Radiometry / Radiotherapy / Reduction / Research and Analysis Methods / Somatostatin / Studies / Synergistic effect / Synergistic effects / Thyroid / Thyroid cancer / Thyroid diseases / Thyroid Neoplasms - diagnosis / Thyroid Neoplasms - metabolism / Thyroid Neoplasms - therapy / Tumors