Banca de DEFESA: IRISLENE COSTA PEREIRA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
DISCENTE: IRISLENE COSTA PEREIRA
DATA: 25/10/2025
HORA: 15:00
LOCAL: DEPARTAMENTO DE BIOFISICA
TÍTULO: Caloric Restriction and Short-Term Fasting in Breast Cancer: Translational Evidence
PALAVRAS-CHAVES: Caloric restriction; Fasting; Cell viability; Mammary neoplasia; Doxorubicin
PÁGINAS: 252
GRANDE ÁREA: Ciências Agrárias
ÁREA: Ciência e Tecnologia de Alimentos
RESUMO:

INTRODUCTION: Breast cancer (BC) is one of the most prevalent malignancies, particularly among women. The triple-negative subtype (TNBC) is notably aggressive and exhibits a high incidence of chemoresistance, presenting a significant challenge in clinical practice. Growing evidence suggests that tumor metabolism can be modulated by nutritional interventions—such as short-term fasting, caloric restriction, and fasting-mimicking diets—offering a promising strategy to overcome therapeutic resistance and improve clinical outcomes. OBJECTIVES: The main objective of this thesis was to investigate the potential of nutritional interventions—specifically cyclical caloric restriction (CCR), fasting-mimicking diets (FMD), and short-term fasting (STS)—to reprogram the metabolism of breast cancer cells and modulate their response to treatments. This research was conducted using a translational approach, encompassing narrative and systematic reviews, as well as experimental studies in vitro, in vivo, and a preliminary clinical trial. METHODOLOGY: This thesis is structured into six chapters, each employing different methodologies. Chapter 1 is a narrative review addressing metabolic alterations in BC, the role of restrictive diets in chemoresistance, and their therapeutic potential. Chapters 2 and 3 consist of two systematic reviews—registered with PROSPERO and conducted according to PRISMA guidelines—evaluating the effects of FMDs in preclinical models and clinical trials, respectively. Chapter 4 presents an in vitro study using the MDA-MB-231 TNBC cell line to assess the effects of STS combined with doxorubicin on cell viability, gene expression, and mitochondrial superoxide production. Chapter 5 details an in vivo study in mice with 4T1-induced breast cancer, investigating the safety and antitumor effects of CCR in combination with doxorubicin. Chapter 6 presents preliminary data from a clinical study involving women with BC, exploring the feasibility and effects of caloric restriction on body composition, quality of life, and emotional well-being. RESULTS: The systematic reviews demonstrated that FMDs can inhibit tumor growth and enhance the efficacy of cancer therapies. The in vitro study showed that STS exerts antitumor effects and, when combined with doxorubicin, increases mitochondrial oxidative stress, induces apoptosis, and causes cell cycle arrest. In the in vivo model, CCR combined with chemotherapy significantly reduced tumor volume and weight, while being safe and well tolerated. Preliminary clinical trial findings indicate that caloric restriction is a feasible and safe intervention for women with breast cancer. Notably, after 42 days of intervention, no significant reduction in body weight was observed—an important clinical consideration in oncology—supporting the safety of the approach. CONCLUSION: This thesis provides strong translational evidence that caloric restriction and short-term fasting represent promising complementary therapeutic strategies. These interventions reprogram tumor metabolism and modulate key signaling pathways, thereby increasing the sensitivity of breast cancer cells—particularly TNBC—to chemotherapy. 

MEMBROS DA BANCA:
Presidente - 2950101 - FRANCISCO LEONARDO TORRES LEAL