The statistical data provided by the Global Burden of Diseases, Injuries, and Risk Factors Study, 2017 suggested that the worldwide rate of demise due to all reasons is 55.9 million with an age-standardized death rate of 737.7 per 100,000 in 2017 (Hong et al., 2022). Gastrointestinal cancers account for 1 in 4 incidences of cancer, and 1 in 3 cancer demises worldwide. Globally, there is a substantial alteration in the estimates of cancer occurrence and demises. Gastric cancer incidence has decreased, but colorectal cancer incidence has increased in formerly low-incidence regions (Arnold et al., 2020). Indeed, the incidences of hepatocellular and pancreatic cancer have increased in some high-income regions. Primary and secondary modes of prevention remain crucial and involve multiple plans such as regulating the consumption of alcohol, and tobacco, controlling obesity, immunizing the masses with hepatitis B virus vaccines, and scheduled screening of patients for colorectal cancers (Blumberg, 2010).

In addition, some frequently occurring gastrointestinal tract cancers such as stomach, colorectal, liver, oesophageal, and pancreatic cancer are the main providers of the seven major causes of cancer-associated mortalities. Comprehensively, gastrointestinal tract cancers are estimated as 36.2% of neoplasms-associated demises (Jardim et al., 2023). Similarly, in China, the statistical data of the year 2015 suggested that five out of six gastrointestinal cancers are the prime reason for cancer-linked demises, excluding lung cancer. The statistics mentioned above have established that the appropriate management of gastrointestinal cancers is required to decrease the total load of cancer-related demises (Chen et al., 2016).

Colon cancer is the second most frequent reason for cancer demise in the United States. With every passing three years, the American Cancer Society provides updated statistical data on colon incidences and mortalities obtained from population-based registries and the National Center for Health Statistics (Rawla et al., 2019a). As per the data updated in 2023, about 153,020 persons will be detected with colon cancer, and 52,550 will expire from this cancer, including 19,550 incidences and 3750 demises in persons of age under 50 years. It has been observed that most incidences and demises are accountable to changeable risk factors, including poor diet, mass consumption of alcohol, lack of physical activity, obesity, and smoking (Simon, 2016). Furthermore, a large colon cancer population could be saved by incorporating usual monitoring, screening, and high-grade therapeutic management (Holt et al., 2009). In sum, although previous year’s statistics have demonstrated a significant fall in occurrences and demises, the diagnosis of colon cancer is continuously shifting toward young age and more advanced stages. Moreover, subsequent investigation is required to explore the underlying cause of high incidences of colon cancer and better therapeutic modalities for various subtypes of this cancer (Samant et al., 2021).

Worldwide, hepatocellular/liver cancer is the sixth most frequently detected cancer, with 841,000 incidences, the fourth prime reason for cancer-related demises diagnosed cancer (841,000 cases), and the fourth leading cause of mortality with 782,000 demises. Like other gastrointestinal cancers, the occurrences and deaths of liver cancer increased by 2–3-fold more in males than females. The epidemiological statistics have suggested that a universal load of hepatocellular carcinoma is more significant in ascending nations as the estimates are larger in Micronesia, Eastern Asia, and Northern Africa, excluding Mongolia, with larger rates of occurrence and demise globally (Mcglynn et al., 2015). Various cancer registries have documented their data which accentuate the alteration in occurrence rates between and within global regions, specifically in Asia. Owing to the improbabilities associated with hepatocellular cancer, occurrence and death patterns are highly correlated and exhibit comparable trends all over the globe (Liu & Liu, 2022). Indeed, national-level patterns in incidence and mortality are quite heterogeneous, whereas the past few decades have witnessed enhancing occurrence rates in different regions of the world, including the United States, Australia, and major regions of Europe. On the other side, declining rates have been noticed in Asian nations like Republic of Korea, Japan, and China (Singal et al., 2020).

Gallbladder carcinoma is the sixth most predominant gastrointestinal cancer and is a highly prevalent cancerous form of the biliary system (Rawla et al., 2019b). As per the Globocon 2020 report, 116,000 new incidences and 84,700 demises of gall bladder cancer were reported (Sung et al., 2021). About 4000 new incidences are detected annually in the United States, setting North America as a low-occurrence place. A larger number of incidences are reported in people over 70 years, and this rate is two or six-fold more frequent in females than males (Ouyang et al., 2021). Globally, substantial heterogeneity in different regions has been observed in the incidences of gall bladder cancer, and this instability corresponds with the prevalence of cholelithiasis (Sharma et al., 2017). The geographic epidemiological data demonstrates that nations like South America, specifically Chile, Bolivia, and Ecuador, along with some areas in northern India, Pakistan, Japan, Korea, and Poland, are distressed by more than average incidences of gall bladder cancer (Singh et al., 2022). Certain risk factors, like a large number of occurrences of gall stones infection with Salmonella, which are well-known for increasing the frequency of gallbladder cancer, are mutual in the above-stated cases (Stinton & Shaffer, 2012). Reports have shown that about 0.3–3.0% of persons undergoing cholecystectomy are detected with gall bladder carcinoma accidentally (Halaseh et al., 2022).

The standard therapeutic strategies broadly utilized for treating and managing gastrointestinal cancers involve surgery, radiotherapy, and chemotherapy (Krasteva & Georgieva, 2022). In the case of colon cancer, surgical intervention and administration of chemotherapeutic drugs are the standard treatment options for the patients. Furthermore, recent times have witnessed the use of targeted therapy as a novel approach which has proven its worth by favorably prolonging the net survival rate of colon cancer patients. There are some achievements with novel agents like cetuximab (anti-EGFR) and bevacizumab (anti-angiogenic agent) obstructing the various crucial signaling cascades along with immune checkpoints evolving unparalleled. Furthermore, in the early stages of hepatocellular carcinoma, liver transplantation, and ablation are primarily utilized as therapeutic options (Deng et al., 2015, Kudo, 2018); however, standard systemic chemotherapy has lost its survival benefits for patients in advanced stages of cancer (Kudo, 2018). Currently, an accrued number of researchers have made considerable progress in interpreting signaling cascades, methods to analyze the progression of tumors, and drugs to obstruct pathway activity, creating possibilities to formulate meticulous therapeutic strategies (Niu et al., 2021). Consequently, different targeted drug agents based on signaling molecules are propitiously endorsed in clinical studies, and molecular targeted therapy has earlier become a landmark for the disease management of hepatocellular carcinoma patients. Furthermore, the conduit for hepatocellular carcinoma is developing towards combinatorial therapeutics with propitious clinical consequences (Goetze, 2015).

In gall bladder, radical surgical resection is an extensive leading therapy still approved for the treatment of gall bladder cancer. Cisplatin, carboplatin and gemcitabine are the major therapeutic modalities for treating advanced stages of gall bladder cancer (Roa et al., 2022, Javle et al., 2014). With the advent of the latest technologies, such as sequencing technology, therapeutical interventions for gall bladder cancer are being continuously upgraded, and the utilization of molecular profiling of gall bladder cancer advocates the evolution and further clinical practice of newly targeted immunotherapeutic drugs (Nakamura et al., 2015, Kumar et al., 2021). Although, in some cases, success has been achieved. Still, the quest is focused on exploring better, safe, and more effective therapeutic modalities for gastrointestinal cancers.

Recently, molecular researchers have deciphered the imperative contribution of major developmental/self-renewable signaling pathways, such as Wnt, Hedgehog, and Notch signaling pathways, in gastrointestinal-related cancers (Kumar et al., 2021). These signaling cascades are found to be associated with the carcinogenesis of multiple solid tumors contributing to the development of cancer (Sever & Brugge, 2015). This book chapter gives its readers an intriguing summary of the latest updates focusing on these signaling pathways and mechanistic insight into gastrointestinal carcinomas. This chapter also gives a pavement for investigating the molecular biological mechanism of different cancers of the gastrointestinal tract and relevant information for developing novel therapeutic strategies against some common gastrointestinal cancers.