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Mechanisms highlighted include modulation of cancer hallmarks and key cellular pathways regulating survival, genome maintenance, proliferation, senescence, and transendothelial migration. Antioxidant phytochemicals reduce reactive oxygen species to limit lipid peroxidation and DNA damage, while checkpoint-driven cell-cycle arrest supports apoptosis and DNA damage responses. 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In vivo and preclinical models show that they do so often by affecting the hallmarks of cancer. Phytochemicals affect key pathways involved in the survival, genome maintenance, proliferation, senescence, and transendothelial migration of cancer cells. Some phytochemicals, namely antioxidants, can scavenge and quench reactive oxygen species (ROS) to prevent lipid peroxidation and DNA damage. They also trigger apoptosis by stopping the cell cycle at checkpoints to initiate the DNA damage response. Numerous in vitro and in vivo studies suggest that phytochemicals hinder cancer onset and progression by modifying major cell signaling pathways such as JAK/STAT, PI3K/Akt, Wnt, NF-kB, TGF-β, and MAPK. It is a well-known fact that the occurrence of cancer is in itself a very intricate process involving multiple mechanisms concurrently. Cancer prevention using phytochemicalsis also an equally complex process that requires investigation and understanding of a myriad of processes going on in the cells and tissues. While many in vitro and preclinical studies have established that phytochemicals may be potential chemopreventive agents of cancer, their role in clinical randomized control trials needs to be established. This paper aims to shed light on the dynamics of chemoprevention using phytochemicals.  \nKeywords  \ncancer, phytochemicals, chemoprevention, antioxidants, signaling pathways, immunotherapy, clinical trials, bioavailability  \nReceived July 18, 2024. Received revised October 11, 2024. Accepted for publication November 11, 2024.  \nIntroduction  \nCancer is a disease caused by abnormal growth and uncontrolled division of cells. It can initiate at any organ and can metastasize to remotely located organs. A diverse array of causative agents aid in causing cancer, ranging from physical agents, namely ultraviolet rays and ionizing radiation, to chemical agents like asbestos, alcohol, and tobacco smoke, and biological agents such as certain bacteria, viruses, and parasites.1 According to the International Agency for  \nResearch on Cancer (IARC), cancer is among the leading causes of death worldwide in 2022 resulting in 9.7 million fatalities. About 1 in 5 people develop cancer in their lifetime, and approximately 1 in 9 males and 1 in 12 females die from the cancer.2 In recent times, the mortality rate from cancer has decreased considerably owing to the discoveries in molecular biology, recombinant DNA technology, and immunology.3,4 Reduction in the number of smokers, maintenance of healthy eating habits, enhancement of living standards and  \n1 Department of Biotechnology, Kathmandu University, Dhulikhel, Nepal  \nCorresponding Author:  \nHitesh Kumar Bhattarai, School of Science, Departement of Biotechnology, P. O. Box 6250, Dhulikhel, Nepal.  \nEmail: hitesh321@gmai[l.com](l.com)  \nCreative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons  \nAttribution-NonCommercial 4.0 License ([https://creativecommons.org/licenses/by-nc/4.0/](https://creativecommons.org/licenses/by-nc/4.0/)) which permits non-commercial use,  \nreproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ([https://us.sagepub.com/en-us/nam/open-access-at-sage](https://us.sagepub.com/en-us/nam/open-access-at-sage)).  \nenvironmental facilities, and focus of atten","cbCaisNprmkHuqX2","https://ap.wps.com/l/cbCaisNprmkHuqX2","pdf",2126054,38,"English","# Abstract\n# Introduction\n## Cancer causes and global burden\n## Diet, phytochemicals, and cancer hallmarks\n## Types and mechanisms of chemopreventive agents","[{\"question\":\"How do phytochemicals help prevent cancer in preclinical models?\",\"answer\":\"They influence cancer hallmarks and multiple pathways controlling survival, genome maintenance, proliferation, senescence, and transendothelial migration. Some antioxidants reduce reactive oxygen species to limit lipid peroxidation and DNA damage.\"},{\"question\":\"What role do antioxidant phytochemicals play?\",\"answer\":\"Antioxidant phytochemicals scavenge and quench reactive oxygen species, which helps prevent lipid peroxidation and DNA damage. They also support apoptosis by engaging checkpoint-related DNA damage responses.\"},{\"question\":\"Why is clinical randomized trial evidence important?\",\"answer\":\"Many in vitro and in vivo studies suggest chemopreventive potential, but clinical randomized control trials are needed to confirm their role in humans and establish evidence beyond preclinical findings.\"}]","Phytochemicals in Cancer Chemoprevention - Preclinical and Clinical Studies - Cancer Control Volume 31 - 1 | PDF",1789999664,96]