Unconventional therapies for cancer treatment

• Autores: Tatiana Paulina Grazioso Javier
• Directores de la Tesis: Nabil Djouder (dir. tes.)
• Lectura: En la Universidad Autónoma de Madrid ( España ) en 2022
• Idioma: inglés
• Número de páginas: 247
• Títulos paralelos:
  • Terapias no convencionales para el tratamiento del cáncer
• Tribunal Calificador de la Tesis: Francisco Xavier Real Arribas (presid.), Guillermo de Cárcer Díez (secret.), Juan Méndez Zunzunegui (voc.), Krishna Seshu Tummala (voc.), Miguel León Arellano (voc.)
• Programa de doctorado: Programa de Doctorado en Biociencias Moleculares por la Universidad Autónoma de Madrid
• Materias:
  • Química
    • Bioquímica
• Enlaces
  • Tesis en acceso abierto en: Biblos-e Archivo
• Resumen

  • Together with lack of prevention and late detection, one of the main limitations in cancer treatment is the lack of personalized therapeutical options. Though hormone, immunotherapy and targeted therapy have significantly revolutionized cancer treatment, primary therapies still rely on surgical procedures, chemotherapy and radiotherapy. Thus, we aim to understand two unconventional approaches for the prevention and treatment of cancers driven by oncogene-induced DNA damage. To simplify, we branched our study to 1) elucidate the role of temperature for the treatment of hepatocellular carcinoma (HCC) and 2) elucidate the beneficial and detrimental effects of vitamin B9 in colorectal cancer (CRC).

    Part 1: Multiple diseases, such as cancer, are an inherent part of the aging process. However, the mechanisms predisposing disease upon aging are yet unclear. Among the proposed mechanisms, the age-dependent decline in NAD+ has been shown to alter cellular homeostasis and DNA integrity increasing disease susceptibility; while, restoring NAD+ revokes these phenotypes. Thus, NAD+ reduction may be the central mechanism linking aging and its associated pathologies. Even though B3 vitamers are the most well-known NAD+ boosters, calorie restriction (CR) has been shown to boost NAD+ providing health-enhancing properties. Moreover, this increase was associated with a decrease in body temperature, suggesting a possible correlation between NAD+ and temperature, which has shown similar healthenhancing effects. In this thesis, we elucidate the chemoprotective properties of temperature, and performed long-term cold exposure treatments in oncogene-induced hepatocarcinogenesis, describing the tumor-preventive properties of cold, by increasing life expectancy and slowing down the progression and the aggressiveness of the disease, preventive thus, the development of aggressive HCC.

    Part 2: The intestinal mucosa is highly susceptible to malignant transformation due to its high rate of proliferation and regeneration. Thus, maintaining intestinal homeostasis through the proper regulation and integration of several pathways is strictly required. Among these pathways, the one carbo-metabolism, which requires vitamin B9, plays an essential role in maintaining DNA integrity by favoring nucleotide synthesis. Since oncogene-induced DNA damage is a significant trigger of tumorigenesis, favoring the accumulation of DNA lesions, mutations and hyperproliferation, proper DNA repair upon the first driving events is a determinant point in tumor prevention. Hence, vitamin B9 supplementation could favor DNA repair and integrity. Here, we elucidate that vitamin B9 has a dual role based on the tumors etiology. Thus, vitamin B9 may act as a chemoprotective agent in CRC; or favor oncogenesis. Highlighting the importance of the genetic background in tumor behavior and response to conventional therapies