Significant changes in diet, environment, and population increase gastrointestinal cancer morbidity. A growing number of novel biomarkers and underlying mechanisms are being elucidated, some of which may even conflict with assumptions of past decades. Therefore, collecting recent findings on novel diagnostic/prognostic factors, biomarkers, and/or risk factors in gastrointestinal cancers is a prerequisite for a better understanding of the disease. Despite remarkable progressions in surgical treatments and chemotherapies, the prognosis of gastrointestinal cancer is far from satisfactory due to the high occurrence of drug resistance. Based on the identification of novel biomarkers as well as their underlying mechanisms, targeted drug development will provide significant complementary therapeutic effects to conventional chemoradiotherapies. High-throughput methods such as next-generation sequencing on RNA level and mass spectrometry on protein/lipid/metabolite level serve as efficient strategies for biomarker identification and drug development. This Research Topic aims at presenting recent advances on gastrointestinal cancer biomarkers and their underlying functional mechanisms, providing a better understanding of carcinogenesis, tumor progression, tumor relapse, as well as drug resistance. This will subsequently contribute to the development of novel therapeutic interventions targeting gastrointestinal cancers, thus improving patients' outcomes.

Gastrointestinal (GI) cancers, including gastric cancer, colon cancer, liver cancer, esophageal cancer, and pancreatic cancer, seriously threaten the health of human beings worldwide with a high rate of morbidity and mortality. The clinical successes achieved with immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 and CTLA-4 have opened a new cancer therapy era and brought new hope to cancer patients. However, the overall response rate (ORR) of ICI monotherapy in the non-selective population is only about 20%, in which some patients subsequently develop immunotherapy resistance. Moreover, the remaining 70-80% of patients displayed primary resistance to ICIs, and a few patients even experienced hyper progression disease (HPD). Although PD-L1 expression, mismatch repair deficient (MMRd), high tumor mutational burden (TMB-H) , high homologous recombination deficiency (HRD), and tumor infiltrated immune cells (TILs) are known as effective biomarkers for immunotherapy, growing studies have reported that ICIs could not improve the OS of all patients with PD-L1 expression higher than 50%, and the ORR of MSI-H patients was only about 60%, whereas some patients with low PD-L1 expression or MSS could still benefit from immunotherapy, indicating the complexity of ICI resistance. Therefore, it is of great importance and significance to explore the prediction biomarkers for primary or acquired immunotherapy resistance and elucidate their underlying molecular mechanisms and develop reversal strategies. Due to the multiple steps of the cancer immune cycle and complex immune microenvironment, any disorders of immune cell infiltration or T cell activation, such as lack of antigens and/or their presentation, lack of response to antigen presentation, and T cell priming, could contribute to ICI resistance. The combination with anti-angiogenesis therapy, radiotherapy, chemotherapy, and other ICIs has improved the efficacy of ICI therapy to some extent in the clinic. Although numerous studies related to ICI resistance were reported in GI cancers, due to the strong spatial/temporal heterogeneity and the complex immune microenvironment in different kinds of GI cancers and different individuals, many questions about ICI resistance and reversal strategies remain unsolved. The aim of this Research Topic is to provide a forum to exhibit the latest research achievement related to the exploration of biomarkers for immunotherapy resistance including HPD and the underlying molecular mechanisms, as well as the development of reversal strategies in GI cancers. We hope this Research Topic will lead to a better understanding of precision cancer immunotherapy and provide useful clues for clinical application to benefit more GI cancer patients with immunotherapy.

Drug Resistance in Colorectal Cancer: Molecular Mechanisms and Therapeutic Strategies, Volume Eight, summarizes the molecular mechanisms of drug resistance in colorectal cancer, along with the most up-to-date therapeutic strategies available. The book discusses reasons why colorectal tumors become refractory during the progression of the disease, but also explains how drug resistance occurs during chemotherapy. In addition, users will find the current therapeutic strategies used by clinicians in their practice in treating colorectal cancer. The combination of conventional anticancer drugs with chemotherapy-sensitizing agents plays a pivotal role in improving the outcome of colorectal cancer patients, in particular those with drug-resistant cancer cells. From a clinical point-of-view, the content of this book provides clinicians with updated therapeutic strategies for a better choice of drugs for drug-resistant colorectal cancer patients. It will be a valuable source for cancer researchers, oncologists and several members of biomedical field who are dedicated to better treat patients with colorectal cancer. - Presents a systemic summary of molecular mechanisms for a quick and in-depth understanding - Updates current trends in the field with pioneering information on drug resistance - Encompasses both basic and clinical approaches for a better understanding of unsolved problems from a holistic point-of-view

Gastrointestinal malignancies encompass a large number of tumor types, and collectively are responsible for a significant portion of new cancer cases annually. According to the IARC database, colorectal cancer alone is responsible for approximately 10% of new cases of cancer worldwide annually. There is significant heterogeneity across the various tumor types, with different pathways and factors involved in oncogenesis, as well as varying degrees of prognosis depending on the tumor type. Non-coding RNAs (ncRNAs) contribute to a significant portion of the human transcriptome, and of particular interest are the micro-RNAs (miRNAs), long ncRNAs (lncRNAs), and circular ncRNAs (circRNAs). With the advent of next-generation sequencing and new technologies such a minimally invasive biopsy techniques, there is a growing body of evidence elucidating the role of ncRNAs in the progression of various form of gastrointestinal cancers. Furthermore, in addition to their relevance to cancer progression, these ncRNAs have important potential as biomarkers and prognostic markers for various GI cancers.

This book describes various novel biomarkers for the early diagnosis of gastrointestinal (GI) cancers. It also highlights recent advances in understanding the role of molecular markers and biomarkers, such as volatile biomarkers, serum biomarkers, predictive and prognostic molecular markers for the early detection of GI cancers. Further, it discusses novel biomarkers, including circulating microRNAs, serum microRNA and plasma microRNA in GI cancer. The book presents breakthrough technologies like ultra-sensitive nano-chips, nanosensors, nanodevices, biosensors, electrochemical biosensors, optical biosensors, DNA biosensors, synthetic biology devices, and 'omics' technologies for the early diagnosis of gastrointestinal cancer. In addition it examines the potential of genome-wide association studies, big data analytics, computation biology, systems biology, and nanotechnology for early diagnostics and therapeutics for gastrointestinal cancer, with a focus on personalized cancer treatment. The book is a valuable source for researchers and clinicians engaged in detection and diagnosis of gastrointestinal cancers.

Gastrointestinal (GI) cancer, the group of cancers that affect the gastrointestinal tract and other organs that are contained within the digestive system, including the esophagus, pancreas, stomach, colon, rectum, anus, liver, biliary system and small intestine, is the most common malignant diseases with high mortality rates, leading to a substantial burden on public health and healthcare systems around the world. Diverse subtypes of GI cancer impressively exhibit similar characteristics like high frequency oncogenic mutation burden, early metastatic potency, chemo-resistance and immunotherapeutic tolerance indicating a possible unique tumorigenic mechanism.

Gastrointestinal cancers are among the most common cancer types, based on the Cancer Genome Atlas. GI cancers are within the most frequent malignancy, with almost 150.000 new cases in 2020. On one hand a big number of researches are focused on the diagnosis, new diagnostic approaches in upper and lower gastrointestinal tract cancers. On the other hand in the last 10 years several papers had been published about the possible therapeutic targets, pointing to precision and personalized medicine.