Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. Recent years have increased significantly our understanding of the genetic alterations that can underlie CRC, but also unraveled the molecular heterogeneity of the disease. Although a simple correlation between genetic pathways, histopathological features and clinical outcome cannot be established, the heterogeneity of CRC is also an opportunity for the development of targeted therapeutic approaches, able to treat an individual tumor with higher efficiency and less toxic side effects. One CRC subtype is characterized by high mutation rates (MSI-H), DNA methylation changes (CIMP-H), mutation in the BRAF oncogene and occurrence of serrated adenomas in the proximal colon. Other groups prevail in the distal colon and consist of either adenomatous polyps with chromosomal aberrations (CIN) and WNT pathway activation, or carry frequent KRAS mutation and metabolic deregulation, or have strong mesenchymal and infiltrative characteristics. Characterization of driver-mutation events in these CRC subgroups has led to the development of specific drugs targeting, for example, the MAPK pathway, but initial clinical trials have revealed unexpected response rates. The collection of chapters in this volume address the biology of specific CRC subtypes and how these may be targeted to improve precision therapy and clinical benefit for the patients.

Emerging technologies in target identification, drug discovery, molecular markers, and imaging are rapidly changing the face of cancer. This book provides a foundation of knowledge in targeted cancer therapeutics. The treatment of cancer is increasingly being individualized, based on an understanding of underlying biologic mechanisms. Poised to change the landscape in oncology, this volume provides a state-of-the-art overview. It will be valuable to practicing and academic physicians, fellows, residents and students, as well as basic scientists, interested in the cancer field.

Development of an effective anticancer therapeutic necessitates the selection of cancer-related or cancer-specific pathways or molecules that are sensitive to intervention. Several such critical yet sensitive molecular targets have been recognized, and their specific antagonists or inhibitors validated as potential therapeutics in preclinical models. Yet, majority of anticancer principles or therapeutics show limited success in the clinical translation. Thus, the need for the development of an effective therapeutic strategy persists.

“Altered energy metabolism” in cancer is one of the earliest known biochemical phenotypes which dates back to the early 20th century. The German scientist, Otto Warburg and his team (Warburg, Wind, Negelein 1926; Warburg, Wind, Negelein 1927) provided the first evidence that the glucose metabolism of cancer cells diverge from normal cells. This phenomenal discovery on deregulated glucose metabolism or cellular bioenergetics is frequently witnessed in majority of solid malignancies. Currently, the altered glucose metabolism is used in the clinical diagnosis of cancer through positron emission tomography (PET) imaging. Thus, the “deregulated bioenergetics” is a clinically relevant metabolic signature of cancer cells, hence recognized as one of the hallmarks of cancer (Hanahan and Weinberg 2011). Accumulating data unequivocally demonstrate that, besides cellular bioenergetics, cancer metabolism facilitates several cancer-related processes including metastasis, therapeutic resistance and so on. Recent reports also demonstrate the oncogenic regulation of glucose metabolism (e.g. glycolysis) indicating a functional link between neoplastic growth and cancer metabolism. Thus, cancer metabolism, which is already exploited in cancer diagnosis, remains an attractive target for therapeutic intervention as well. The Frontiers in Oncology Research Topic “Cancer Metabolism: Molecular Targeting and Implications for Therapy” emphases on recent advances in our understanding of metabolic reprogramming in cancer, and the recognition of key molecules for therapeutic targeting. Besides, the topic also deliberates the implications of metabolic targeting beyond the energy metabolism of cancer. The research topic integrates a series of reviews, mini-reviews and original research articles to share current perspectives on cancer metabolism, and to stimulate an open forum to discuss potential challenges and future directions of research necessary to develop effective anticancer strategies. Acknowledgment I sincerely thank the Frontiers for providing the opportunity and constant support throughout the process of this research topic and eBook production. I gratefully acknowledge all the authors for their valuable contributions. Finally, I would like to thank my brother, Saravana Kumar, G.K., whose personal sacrifices and unflinching encouragement made my career in science possible. References: Hanahan D, Weinberg RA. 2011. Hallmarks of cancer: The next generation. Cell. 144(5):646-74. Warburg O, Wind F, Negelein E. 1926. Über den stoffwechsel der tumoren in körper. Klinische Wochenschrift. 5:829-32. Warburg O, Wind F, Negelein E. 1927. The metabolism of tumors in the body. J Gen Physiol. 8(6):519-30.

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.

Colorectal cancer (CRC) is a major health problem because it represents around 10% of all cancers and achieves a worldwide estimate of 1.4 million newly diagnosed cases annually, resulting in approximately 700,000 deaths. Approximately 19-31% of patients present liver metastases. At diagnosis, a further 23-38% will develop extra-hepatic disease. Over the past decade, the widespread use of modern chemotherapeutic and biological agents, combined with laparoscopic surgical techniques, has improved the prognosis of metastatic CRC. A better understanding of the biology of the tumor, along with high efficiency of diagnostic and therapeutic methods, as well as the spread of screening programs, will improve the survival of the CRC patients in the near future.

Molecular Pathology of Neoplastic Gastrointestinal Diseases reviews the molecular aspects that characterize the spectrum of neoplastic conditions that affect the gastrointestinal tract, providing the reader with current up-to-date knowledge. For each disease entity chapters provide reviews on: the molecular basis of the individual disease molecular testing approaches currently available or in development for diagnosis or for gene target characterization for selective targeted therapies recommended guidelines for clinical application of molecular tests are included whenever available molecular testing for hereditary predisposition or disease risk animal models and cell culture models of disease

Download the ebooks for this Research Topic: Volume I.A: ¦PDF¦ ¦EPUB Volume I.B: ¦PDF¦ ¦ EPUB Hepatobiliary tumor, mainly including hepatocellular carcinoma, cholangiocarcinoma and gallbladder cancer, is a group of highly aggressive malignancies. Hepatocellular carcinoma, cholangiocarcinoma and gallbladder cancer have different biological characters, histopathological traits, and treatment strategies, but have similar clinical features such as silent early symptom and extremely poor prognosis. The diagnostic, predictive or prognostic tumor biomarkers of hepatobiliary cancers are in unmet need. In contrast to the poor outcome, the treatment options to hepatobiliary cancers are very limited. It is still controversial about the effects of chemotherapy and radiotherapy of hepatobiliary cancer. FDA-approved targeted drugs are only Sorafenib and Lenvatinib for hepatocellular carcinoma, and Pemigatinib for cholangiocarcinoma. Unfortunately, these drugs are only effective for 5%-30% patients. Therefore, more attention should be called upon on investigating effective biomarkers and drug targets, stratifying high-risk patients, guiding precise treatments, and developing therapeutic strategies for hepatobiliary cancers. This Research Topic aims at discussing the current knowledge and proceedings of diagnostic, predictive and prognostic tumor biomarkers in hepatobiliary cancer, and presenting the recent advances on new drug targets and potential targeted therapies of hepatobiliary cancer. We welcome submissions of Review, Mini-Review, Clinical Trial and Original Research articles covering, but not limited to, the following topics: 1. new diagnostic/prognostic factors, biomarkers and/or risk factors in hepatobiliary tumors 2. new drug targets, and oncogenic or tumor suppressive molecular mechanism of the novel targets 3. new intervention or targeted therapy in hepatobiliary tumors 4. new findings of bioinformatics or high-throughput methods such as mass spectrometry and genome-wide association studies or which may help screen the potential biomarkers of hepatobiliary tumors 5. clinical studies such as cohort study or RCT to identify new risks or treatment therapies in hepatobiliary tumors 6. basic, pharmacological, preclinical or clinical study of potential drugs targeting hepatobiliary tumors Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.

This volume will bring together a review of research being carried out by international experts in this field, detailing treatment and research approaches in several forms of malignant brain tumors. These include glioblastoma (GBM), a highly aggressive and fatal form of astrocytoma which accounts for 80% of newly diagnosed brain tumor patients per year, and meningioma, of which 10% are malignant and extremely resistant to targeted therapies. The volume will also include a discussion of methods to overcome blood-brain barrier exclusion for more efficient targeted drug delivery in all forms of brain cancer treatment. The volume will include information on the repurposing of drugs in an attempt to circumvent drug resistance, use of small molecule inhibitors in GBM treatment, mechanisms of secondary brain metastasis, drug resistance, and state-of-the-art imaging of targeted therapies.