21 January 2019

In preclinical prostate carcinoma in the bone, Rad-223 eradicated effectively micro-tumors but macro-tumors persisted and expanded. The data point to application of Rad-223 in secondary prevention of early bone-metastatic disease and regimens co-targeting the tumor core.

Peter Friedl, theme Cancer development and immune defense, and colleagues, published these findings in the Journal of the National Cancer Institute (JNCI).

Bone-targeting radiotherapy with Radium-223 (Rad-223), a radioisotope emitting genotoxic alpha-radiation with limited tissue penetrance (∼100 µm), prolongs the survival of patients with metastatic prostate cancer (PCa). Confoundingly, the clinical response to Rad-223 is often followed by detrimental relapse and progression, and whether Radium-223 causes tumor-cell directed cytotoxicity in vivo remains unclear. In a joint effort between the Radboudumc and the MD Anderson Cancer Center, they show that limited radiation penetrance in situ defines outcome. 
 
They tested the Radium-223 overall response in prostace cancer in mouse bones and applied intravital microscopy and in silico modeling to predict Rad-223 effectiveness in lesions of different sizes. Rad-223 caused profound cancer cell lethality along the bone interface but not the more distant tumor core. In silico simulations predicted greater efficacy of Rad-223 on single-cell lesions (eradication rate: 88.0%) and minimal effects on larger tumors (no eradication, 16.2% growth reduction in tumors of 27,306 cells), further confirmed in vivo tumors in mice. Micro-tumors showed severe growth delay or eradication in response to Rad-223, whereas macro-tumors persisted and expanded. 
 
The relative inefficacy in controlling large tumors points to application of Rad-223 in secondary prevention of early bone-metastatic disease and regimens co-targeting the bone niche together with the tumor core.

Related news items


The first Radboud Nanomedicine community networking event

14 February 2019

On 7 February 2019 the first Radboud Nanomedicine community networking event took place. The goal of the event was to bring together all those working in the field of nanomedicine at the Radboud University and Radboudumc, irrespective of the theme in which the research is performed.

read more

Research Integrity Round: The ConScience App 15 February 2019

14 February 2019

To introduce the new Netherlands Code of Conduct for Research Integrity we invited ‘Het Acteursgenootschap’ to perform ‘The ConScience App’, a theatre piece designed to move the debate on scientific knowledge. All Radboudumc researchers are invited to attend this event.

read more

Gene involved in colorectal cancer also causes breast cancer

14 February 2019

Judith Grolleman, Nicoline Hoogerbrugge and Richarda de Voer, theme Tumors of the digestive tract, published in Cancer Cell that mutations in the NTHL1 gene, previously associated with colorectal cancer, also cause breast cancer and other types of cancer.

read more

Endometrial natural killer cells remember previous pregnancy

11 February 2019

Dorien Feyaerts, theme Inflammatory diseases, showed that pregnancy induces a memory phenotype on endometrial natural killer cells. However, previous CMV infection is a prerequisite for this memory induction. They published their findings in Cellular and Molecular Immunology.

read more

A personal touch of Iris Nagtegaal

10 February 2019

In order to promote interaction amongst colleagues within RIMLS, we have a ‘personal touch’ series setting employees in the spotlight. A light-hearted manner to learn about the colleagues you know and those you don’t! This week: Iris Nagtegaal.

read more

ZonMw TOP grant to uncover the dormancy of malaria parasites

7 February 2019

Richard Bartfai, theme Infectious diseases and global health, and Clemens Kocken (BPRC) received 675,000 euros from ZonMw to uncover the molecular mechanisms underlying dormancy of malaria parasites, a major obstacle to efficient treatment of P. vivax malaria.

read more