DSpace Collection:https://hdl.handle.net/10171/189922024-03-29T12:24:05Z2024-03-29T12:24:05ZStratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanismhttps://hdl.handle.net/10171/690802024-02-19T06:06:20Z2022-01-01T00:00:00ZTitle: Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism
Abstract: Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in
preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized
the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understand-
ing of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable
targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models
of brain metastasis resistant to WBRT, we identified activation of the S100A9–RAGE–NF-κB–JunB pathway in brain metastases
as a potential mediator of resistance in this organ. Targeting this pathway genetically or pharmacologically was sufficient to
revert the WBRT resistance and increase therapeutic benefits in vivo at lower doses of radiation. In patients with primary mela-
noma, lung or breast adenocarcinoma developing brain metastasis, endogenous S100A9 levels in brain lesions correlated with
clinical response to WBRT and underscored the potential of S100A9 levels in the blood as a noninvasive biomarker. Collectively,
we provide a molecular framework to personalize WBRT and improve its efficacy through combination with a radiosensitizer
that balances therapeutic benefit and toxicity.2022-01-01T00:00:00ZRescuing Spanish Radiation Therapy: The Role of Leadership and Opportunityhttps://hdl.handle.net/10171/690652024-02-19T06:06:16Z2018-01-01T00:00:00ZTitle: Rescuing Spanish Radiation Therapy: The Role of Leadership and Opportunity
Abstract: Radiation therapy is a major cornerstone in cancer treat-
ment. Organ preservation in early tumors, treatment of
locally advanced cancers, and the curative or palliative
treatment of metastatic disease is possible thanks to the
efforts of radiation oncologists in caring for their patients
and to the tremendous technological advances available in
recent decades. Unfortunately, much of this good news is
unknown and unnoticed by either the general population,
the media, or by politicians. Furthermore, globally there is
a wide variation in resources and access to radiation therapy
by countries, regions, and even within cities (1).2018-01-01T00:00:00ZImmune mechanisms mediating abscopal effects in radioimmunotherapyhttps://hdl.handle.net/10171/690582024-02-19T06:06:12Z2019-01-01T00:00:00ZTitle: Immune mechanisms mediating abscopal effects in radioimmunotherapy
Abstract: Radiotherapy of cancer has been traditionally considered as a local therapy without noticeable effects outside the
irradiated fields. However, ionizing radiation exerts multiple biological effects on both malignant and stromal
cells that account for a complex spectrum of mechanisms beyond simple termination of cancer cells. In the era
of immunotherapy, interest in radiation-induced inflammation and cell death has considerably risen, since
these mechanisms lead to profound changes in the systemic immune response against cancer antigens. Immuno-
therapies such as immunomodulatory monoclonal antibodies (anti-PD-1, anti-CTLA-4, anti-CD137, anti-OX40,
anti-CD40, anti-TGFβ), TLR-agonists, and adoptive T-cell therapy have been synergistically combined with radio-
therapy in mouse models. Importantly, radiation and immunotherapy combinations do not only act against the
irradiated tumor but also against distant non-irradiated metastases (abscopal effects). A series of clinical trials are
exploring the beneficial effects of radioimmunotherapy combinations. The concepts of crosspriming of tumor
neoantigens and immunogenic cell death are key elements underlying this combination efficacy. Proinflamatory
changes in the vasculature of the irradiated lesions and in the cellular composition of the leukocyte infiltrates in
the tumor microenvironment contribute to raise or dampen cancer immunogenicity. It should be stressed that
not all effects of radiotherapy favor antitumor immunity as there are counterbalancing mechanisms such as
TGFβ, and VEGFs that inhibit the efficacy of the antitumor immune response, hence offering additional therapeu-
tic targets to suppress. All in all, radiotherapy and immunotherapy are compatible and often synergistic
approaches against cancer that jointly target irradiated and non-irradiated malignant lesions in the same patient.2019-01-01T00:00:00ZA proposal for a Geant4 physics list for radiotherapy optimized in physics performance and CPU timehttps://hdl.handle.net/10171/690252024-02-12T06:09:29Z2020-01-01T00:00:00ZTitle: A proposal for a Geant4 physics list for radiotherapy optimized in physics performance and CPU time2020-01-01T00:00:00Z