Thesis

Cancer weapons against neurodegeneration

• Call:

  ProtoTera Call 2023/2

• Academic Year:

  2023

• Supervisor:

  Daniel Galaviz

• Co-Supervisor:

  Federico Herrera

• Host Institution:

  LIP - Laboratório de Instrumentação e Física Experimental de Partículas

• Granting Degree Institution:

  FCUL (Universidade de Lisboa)

• Typology:

  National

• Abstract:

  Proton Radiation Therapy (PRT) is a powerful anticancer tool being the hadrontherapy modality with the strongest growth over the last decades. PRT has the unique capability to confine high-doses in small and deep space regions due to its inverse dose deposition profile. While the reduction of dose in healthy tissue is significant in PRT, its Relative Biological Effectiveness (RBE) is comparable to that of other Radiation Therapy (RT) modalities [1]. Innovative approaches have recently enhanced its RBE, adding boron in low concentrations to the body and activating it through proton-induced reactions [2]. Low-dose RT has an hormetic nature, and it produces a wide variety of non-toxic biological effects that have therapeutic potential beyond killing cancer cells. For example, low-dose RT has been successfully applied to treat peripheral protein aggregation diseases known as amyloidosis, which resemble widespread neurodegenerative disorders such as Alzheimer (AD), Parkinson (PD) or Huntington diseases (HD) [3]. Our simulation and experimental preliminary results with conventional RT sources indicate that radiation could actually prevent the formation of amyloid structures. However, the therapeutic potential of both conventional and proton RT has been barely explored in this context. We propose to turn novel and powerful PRT approaches for cancer treatment into weapons against neurodegenerative disorders, targeting toxic amyloids with boron- and fluorine-based compounds [4-6] in combination with low-dose PRT. Our hypothesis is that PRT will reduce the aggregation and toxicity of amyloid structures associated with AD, PD and HD, among other disorders, and significantly increase the RBE. The proposed PhD program will have a strong multidisciplinary component, unifying the fields of nuclear physics, biochemistry and bioimaging to lay the groundwork for an increase in the versatility of future PRT facilities