Advances in molecular genetics have revolutionized our understanding of the pathogenesis, progression, and therapeutic options for treating gastrointestinal (GI) cancers. This chapter provides a comprehensive overview of the molecular landscape of GI cancers, focusing on key genetic alterations implicated in tumorigenesis across various anatomical sites including GIST, colon and rectum, and pancreas. Emphasis is placed on critical oncogenic pathways, such as mutations in tumor suppressor genes, oncogenes, chromosomal instability, microsatellite instability, and epigenetic modifications. The role of molecular biomarkers in predicting prognosis, guiding treatment decisions, and monitoring therapeutic response is discussed, highlighting the integration of genomic profiling into clinical practice. Finally, we address the evolving landscape of precision oncology in GI cancers, considering targeted therapies and immunotherapies.

The term "cancer" refers to the state in which cells in the body develop mutations and lose control over their replication. Malignant cancerous cells invade in various other tissue sites of the body. Chemotherapy, radiation, and surgery are the first-line modalities for the majority of solid cancers. These treatments work by mitigating the DNA damage of cancerous cells, but they can also cause harm to healthy cells. These side effects might be immediate or delayed, and they can cause a high rate of morbidity and mortality. Dietary interventions have a profound impact on whole-body metabolism, including immunometabolism and oncometabolism which have been shown to reduce cancer growth, progression, and metastasis in many different solid tumor models with promising outcomes in early phase clinical studies. Dietary interventions can improve oncologic or quality-of-life outcomes for patients that are undergoing chemotherapy or radiotherapy. In this chapter, we will focus on the impact of nutritional deficiencies, several dietary interventions and their proposed mechanisms which are used as a novel therapy in controlling and managing cancers.

Cancer morbidity and mortality incidence are rapidly increasing over the period of time. Cancer prevention, alongside innovative therapies and earlier detection, is considered a key strategy for reducing the overall cancer burden. Substantial evidence indicates a clear correlation between lifestyle factors and changes in nutrient metabolism. Approximately 5-10% of all cancer cases are attributed to genetic factors, whereas 90-95% are due to environmental and lifestyle factors, suggesting that lifestyle interventions have significant prospects for preventing various cancers. Healthy lifestyle changes, in particular healthy diets, physical activity, staying at a healthy weight, reduction or elimination of tobacco/alcohol consumption, and avoiding exposure to radiation and other carcinogens, are significant factors to be considered to tackle the challenges associated with cancer in modern society. This chapter aims to provide lifestyle intervention strategies to improve cancer prevention and risk reduction while promoting the health of cancer patients. The therapeutic role of some dietary regimens and supplements, as well as complementary and alternative health approaches, in cancer treatment is also discussed.

Gallbladder carcinoma (GBC) is the most common biliary epithelial malignancy, with an estimated incidence of 1.13 cases per 100,000 in the United States (Hundal and Shaffer in Clin Epidemiol 6:99-109, 2014 1; Henley et al. in Cancer Epidemiol Biomarkers Prev 24:1319-1326, 2015 2). The insidious nature and late presentation of this disease place it among the most lethal invasive neoplasms. Gallbladder cancer spreads early by lymphatic or hematogenous metastasis, as well as by direct invasion into the liver. While surgery may be curative at early stages, both surgical and nonsurgical treatments remain largely unsuccessful in patients with more advanced diseases (Rahman et al. in Cancer Med 6:874-880, 2017 3).

Hepatocellular carcinoma (HCC) is the fifth most common cancer in men and the eighth most common cancer in women worldwide. It is also the second leading cause of cancer death worldwide, with 780,000 deaths in 2018. Seventy-two percent of HCC cases occur in Asia, 10% in Europe, 8% in Africa, 5% in North America, and 5% in Latin America (Singal et al. in J Hepatol 72(2):250-261, 2020 [1]).

Cancer, a non-communicable disease with diverse kinds is one of the major global problems with high incidence and no proven method to prevent or treat. Minerals including trace elements are significant micronutrients for preserving the body's typical physiological function. In contrast to extremely processed industrial food, they are rich in natural sources of food and frequently included in nutritional supplements. The daily intake, storage capacities, and homeostasis of micronutrients depend on specific dietary practices in contemporary civilization and can be disturbed by various malignancies. Varied minerals have different effects on the status of cancer depending on how they affect these pathways. The outcomes could differ depending on the mineral such as calcium's supply and the cancer's location. A mineral called zinc helps the immune system function better and aids in wound healing. On the other hand, selenium exhibits anti-oxidant functions and has a dose-response relationship with many cancer types. However, this component can make the patient's condition worse. Although the body produces free radicals when iron is deficient, anaemia affects a patient's quality of life and ability to receive therapy. This chapter compiles the knowledge of minerals connected to unusual accumulation or depletion states in various malignancies.

Gut microbes are important and may play important role in spreading cancers specially the gastrointestinal malignancies preferably colorectal cancers. Gut microbes and diet can influence the tissues in gastrointestinal tract increasing the risk of cancer spread. Insufficient nutrient intake and imbalance diet can disturb the microbiome of gastrointestinal tract causing metabolism of xenobiotics which is beneficial as well as detrimental. Dietary imbalance may also weaken the immune system which is another reason for spreading and development of cancers. The triage of gut microbiome, host immune system, and dietary patterns may help the initiation of mechanism of carcinogenesis. In addition to its role in carcinogenesis and tumor development, there is still growing evidence as to how intestinal microflora influences the efficacy and toxicity of chemotherapy and immunotherapy by the gut microbiome. It can therefore be used as a biomarker to predict treatment response or poor response and can also be modified to improve cancer treatment.

This chapter explores the pathologic features of benign and malignant lesions of the pancreas. As pathologic classifications evolve particularly for cystic lesions and neuroendocrine tumors, it is important for physicians who treat patients with gastrointestinal malignance to fully evaluate these pathologic classifications.

In USA, colorectal cancer is the third most commonly diagnosed cancer in men, second in women, as well as the third leading cause of cancer deaths (Siegel et al. in Cancer J Clin 73:1-112, 2023 [109]). Worldwide, colorectal cancer is the second leading cause of death and causes almost 916,000 deaths each year (Ferlay in Global cancer observatory: cancer today. International Agency for Research on Cancer, Lyon, 2020 [28]). Fortunately, due to the colon's surgical and endoscopic accessibility and functional redundancy, colorectal cancer is very treatable. Colonoscopic surveillance has the potential for not only providing tissue for the diagnosis of precancerous polyps and invasive carcinoma, but also preventing development of invasive carcinoma by the removal of precancerous lesions. This chapter discusses the clinical and pathologic features of the spectrum of epithelial, hematolymphoid, and mesenchymal malignant tumors of the colon, rectum, appendix, and anus.

Polyunsaturated fatty acids (PUFAs), notably omega-3 (n-3) and omega-6 (n-6), have received much attention owing to their multifaceted effects not only in the management of diverse pathological conditions but also in the maintenance of overall health of an individual. A disproportionately high n-6 to n-3 ratio contributes to the development of various disorders including cancer, which ranks as a leading cause of death worldwide with profound social and economic burden. Epidemiological studies and clinical trials combined with the animal and cell culture models have demonstrated the beneficial effects of n-3 PUFAs in reducing the risk of various cancer types including breast, prostate and colon cancer. The anti-cancer actions of n-3 PUFAs are mainly attributed to their role in the modulation of a wide array of cellular processes including membrane dynamics, apoptosis, inflammation, angiogenesis, oxidative stress, gene expression and signal transduction pathways. On the contrary, n-6 PUFAs have been shown to exert pro-tumor actions; however, the inconsistent findings and controversial data emphasize upon the need to further investigation. Nevertheless, one of the biggest challenges in future is to optimize the n-6 to n-3 ratio despite the genetic predisposition, age, gender and disease severity. Moreover, a better understanding of the potential risks and benefits as well as the cellular and molecular mechanisms of the basic actions of these PUFAs is required to explore their role as adjuvants in cancer therapy. All these aspects will be reviewed in this chapter.