Dataset Information

Could Protons and Carbon Ions Be the Silver Bullets Against Pancreatic Cancer?

ABSTRACT: Pancreatic cancer is a very aggressive cancer type associated with one of the poorest prognostics. Despite several clinical trials to combine different types of therapies, none of them resulted in significant improvements for patient survival. Pancreatic cancers demonstrate a very broad panel of resistance mechanisms due to their biological properties but also their ability to remodel the tumour microenvironment. Radiotherapy is one of the most widely used treatments against cancer but, up to now, its impact remains limited in the context of pancreatic cancer. The modern era of radiotherapy proposes new approaches with increasing conformation but also more efficient effects on tumours in the case of charged particles. In this review, we highlight the interest in using charged particles in the context of pancreatic cancer therapy and the impact of this alternative to counteract resistance mechanisms.

SUBMITTER: Huart C

PROVIDER: S-EPMC7369903 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Could Protons and Carbon Ions Be the Silver Bullets Against Pancreatic Cancer?

Huart Camille C Chen Jia-Wei JW Le Calvé Benjamin B Michiels Carine C Wéra Anne-Catherine AC

International journal of molecular sciences 20200704 13

Pancreatic cancer is a very aggressive cancer type associated with one of the poorest prognostics. Despite several clinical trials to combine different types of therapies, none of them resulted in significant improvements for patient survival. Pancreatic cancers demonstrate a very broad panel of resistance mechanisms due to their biological properties but also their ability to remodel the tumour microenvironment. Radiotherapy is one of the most widely used treatments against cancer but, up to no ...[more]

PMID: 32635552

Similar Datasets

Project description:PurposeThis work presents the validation of an analytical pencil beam dose calculation algorithm in a commercial treatment planning system (TPS) for carbon ions by measurements of dose distributions in heterogeneous phantom geometries. Additionally, a comparison study of carbon ions versus protons is performed considering current best solutions in commercial TPS.MethodsAll treatment plans were optimized and calculated using the RayStation TPS (RaySearch, Sweden). The dose distributions calculated with the TPS were compared with measurements using a 24-pinpoint ionization chamber array (T31015, PTW, Germany). Tissue-like inhomogeneities (bone, lung, and soft tissue) were embedded in water, while a target volume of 4 x 4 x 4 cm3 was defined at two different depths behind the heterogeneities. In total, 10 different test cases, with and without range shifter as well as different air gaps, were investigated. Dose distributions inside as well as behind the target volume were evaluated.ResultsInside the target volume, the mean dose difference between calculations and measurements, averaged over all test cases, was 1.6% for carbon ions. This compares well to the final agreement of 1.5% obtained in water at the commissioning stage of the TPS for carbon ions and is also within the clinically acceptable interval of 3%. The mean dose difference and maximal dose difference obtained outside the target area were 1.8% and 13.4%, respectively. The agreement of dose distributions for carbon ions in the target volumes was comparable or better to that between Monte Carlo (MC) dose calculations and measurements for protons. Percentage dose differences of more than 10% were present outside the target area behind bone-lung structures, where the carbon ion calculations systematically over predicted the dose. MC dose calculations for protons were superior to carbon ion beams outside the target volumes.ConclusionThe pencil beam dose calculations for carbon ions in RayStation were found to be in good agreement with dosimetric measurements in heterogeneous geometries for points of interest located within the target. Large local discrepancies behind the target may contribute to incorrect dose predictions for organs at risk.

Project description:Radiotherapy is a cornerstone of cancer therapy. The recently established particle therapy with raster-scanning protons and carbon ions landmarks a new era in the field of high-precision cancer medicine. However, molecular mechanisms governing radiation induced intracellular signaling remain elusive. Here, we present the first comprehensive proteomic and phosphoproteomic study applying stable isotope labeling by amino acids in cell culture (SILAC) in combination with high-resolution mass spectrometry to decipher cellular response to irradiation with X-rays, protons and carbon ions. At protein expression level limited alterations were observed 2 h post irradiation of human lung adenocarcinoma cells. In contrast, 181 phosphorylation sites were found to be differentially regulated out of which 151 sites were not hitherto attributed to radiation response as revealed by crosscheck with the PhosphoSitePlus database.Radiation-induced phosphorylation of the p(S/T)Q motif was the prevailing regulation pattern affecting proteins involved in DNA damage response signaling. Because radiation doses were selected to produce same level of cell kill and DNA double-strand breakage for each radiation quality, DNA damage responsive phosphorylation sites were regulated to same extent. However, differential phosphorylation between radiation qualities was observed for 55 phosphorylation sites indicating the existence of distinct signaling circuitries induced by X-ray versus particle (proton/carbon) irradiation beyond the canonical DNA damage response. This unexpected finding was confirmed in targeted spike-in experiments using synthetic isotope labeled phosphopeptides. Herewith, we successfully validated uniform DNA damage response signaling coexisting with altered signaling involved in apoptosis and metabolic processes induced by X-ray and particle based treatments.In summary, the comprehensive insight into the radiation-induced phosphoproteome landscape is instructive for the design of functional studies aiming to decipher cellular signaling processes in response to radiotherapy, space radiation or ionizing radiation per se Further, our data will have a significant impact on the ongoing debate about patient treatment modalities.

Dataset Information

Could Protons and Carbon Ions Be the Silver Bullets Against Pancreatic Cancer?

Publications

Could Protons and Carbon Ions Be the Silver Bullets Against Pancreatic Cancer?

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets