Endothelin inhibitors for advanced prostate cancer

This is the protocol for a review and there is no abstract. The objectives are as follows: Our review aims to determine the effectiveness and adverse effects of endothelin inhibitors for advanced prostate cancer. The primary objectives are to assess the effect of endothelin inhibitors on overall survival, prostate cancer-speci?c survival, and progression-free survival. The secondary objectives are to determine: 1. the frequency of adverse events; 2. the effect of treatment on target lesions identi?ed by radiological imaging; 3. the effect of treatment on molecular biomarkers, including PSA and bone alkaline phosphatase; 4. the impact on quality of life

Design and conduct of early-phase radiotherapy trials with targeted therapeutics: Lessons from the PRAVO experience

AbstractNew strategies to facilitate the improvement of physical and integrated biological optimization of high-precision treatment protocols are an important priority for modern radiation oncology. From a clinical perspective, as knowledge accumulates from molecular radiobiology, there is a complex and exciting opportunity to investigate novel approaches to rational patient treatment stratification based on actionable tumor targets, together with the appropriate design of next-generation early-phase radiotherapy trials utilizing targeted therapeutics, to formally evaluate relevant clinical and biomarker endpoints. A unique aspect in the development pathway of systemic agents with presumed radiosensitizing activity will also be the need for special attention on patient eligibility and the rigorous definition of radiation dose–volume relationships and potential dose-limiting toxicities. Based on recent experience from systematically investigating histone deacetylase inhibitors as radiosensitizing agents, from initial studies in preclinical tumor models through the conduct of a phase I clinical study to evaluate tumor activity of the targeted agent as well as patient safety and tumor response to the combined treatment modality, this communication will summarize principles relating to early clinical evaluation of combining radiotherapy and targeted therapeutics

Exposure to low dose ionising radiation: Molecular and clinical consequences

•Low dose hyper-radiosensitivity has been demonstrated in 75% of the 50 mammalian normal and malignant cells tested to date.•Low dose hyper-radiosensitivity is induced by a variety of radiation qualities.•Low dose hyper-radiosensitivity is associated with defective double strand breaks DNA repair pathways.•The clinical relevance of Low dose hyper-radiosensitivity in radiation oncology is a matter of debate. This review article provides a comprehensive overview of the experimental data detailing the incidence, mechanism and significance of low dose hyper-radiosensitivity (HRS). Important discoveries gained from past and present studies are mapped and highlighted to illustrate the pathway to our current understanding of HRS and the impact of HRS on the cellular response to radiation in mammalian cells. Particular attention is paid to the balance of evidence suggesting a role for DNA repair processes in the response, evidence suggesting a role for the cell cycle checkpoint processes, and evidence investigating the clinical implications/relevance of the effect