Chapters authored
Glucose Metabolism and Carcinogenesis: The Impact of the Tumor Suppressor p53
The tumor suppressor protein, p53 responds to cellular stress such as DNA damage, oncogenic activation and hypoxia by transactivating downstream genes that are responsible for apoptosis, DNA repair, senescence, cell cycle arrest and cell cycle progression. However, emerging trends show that p53 also plays multifaceted roles in regulating glucose metabolism. It promotes oxidative phosphorylation, suppresses glycolysis at multiple points as well as controlling glutamine and lipid metabolism. Current findings suggest that p53 actions have potential to influence the Warburg Effect, that is, characteristic of cancer cells. The Warburg phenomenon is characterized by their preference for glycolysis to oxidative phosphorylation for ATP generation, irrespective of adequate oxygen supply. This is often in concomitance with enhanced glucose uptake and leads to increased lactate production and anabolic processes such as lipid synthesis and de novo nucleic acid synthesis. The molecular underpinnings of the Warburg Effect are still poorly understood. These important differences between cancer and normal cells have induced interest in glucose metabolism as a drug target. This chapter focuses on the influence p53 exerts on glucose metabolism as well as on the implications of the Warburg phenomenon in carcinogenesis and a review of the ever-increasing number of p53 regulators.
Part of the book: Neoplasm
Two-Dimensional (2D) and Three-Dimensional (3D) Cell Culturing in Drug Discovery
Cell culture is an indispensable in vitro tool used to improve our perception and understanding of cell biology, the development of tissue engineering, tissue morphology, mechanisms of diseases and drug action. Efficient cell culturing techniques both in vitro and in vivo allow researchers to design and develop new drugs in preclinical studies. Two-dimensional (2D) cell cultures have been used since 1900s and are still a dominant method in many biological studies. However, 2D cell cultures poorly imitate the conditions in vivo. Recently three-dimensional (3D) cell cultures have received remarkable attention in studies such as drug discovery and development. Optimization of cell culture conditions is very critical in ensuring powerful experimental reproducibility, which may help to find new therapies for cancer and other diseases. In this chapter, we discuss the 2D and 3D cell culture technologies and their role in drug discovery.
Part of the book: Cell Culture
Current Advances in Immune Checkpoint Therapy
Although immune checkpoint inhibitors (ICIs) have shown survival benefits for patients with metastatic cancers, some challenges have been under intense study in recent years. The most critical challenges include the side effects and the emergence of resistance. Potential opportunities exist to develop personalized immune checkpoint inhibitor therapy based on biomarker discovery. Combinational therapy involving immune checkpoint inhibitors and other forms of anticancer therapies has varied success. This chapter reviews drugs currently undergoing Phase III clinical trials and others that are FDA-approved. We take a critical look at the combinational strategies and address the ever-present challenge of resistance. Moreover, we review and evaluate the discovery of biomarkers and assess prospects for personalized immune checkpoint therapy.
Part of the book: Immune Checkpoint Inhibitors