Hepatocellular Cancer

Challenges in the Management of Hepatoblastoma

Hepatoblastoma is the third most common pediatric tumor of the abdomen with an incidence of about 1.2-1.5 cases/million population/year. It has been associated with various genetic conditions, such as familial adenomatous polyposis, Beckwith- Wiedemann syndrome and Edwards syndrome, while genetic mutations of the Wnt signaling pathway are also frequently seen. The different staging systems and treatment approaches of the four hepatoblastoma study groups, International childhood liver tumors strategy group, Children’s Oncology Group, German Society for Pediatric Oncology, and Japanese Study Group for Pediatric Liver Tumors, led to different outcomes among the various trials published over the years. Some groups tended to follow a protocol of an upfront surgical resection, while others suggested neoadjuvant chemotherapy to all patients. Now these groups try to come on the same page by initiating an international collaborative attempt to pool previously published data, as well as to classify future patients into risk-stratified groups that would determine treatment options and facilitate improved survival outcomes. The aim of this chapter is to review the general characteristics of hepatoblastoma, the various treatments implemented over the last years, as well as the challenges in management that its rarity and discrepancies among the study groups pose.

Current and Emerging Cancer Therapies for Treatment of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related deaths worldwide, especially in Asia. Late diagnosis and/or underlying cirrhosis, and limited treatment options with marginal clinical benefit are the reasons for its dismal prognosis. Surgical resection and liver transplantation are curative treatment options but are suitable for patients with small tumours or well-compensated liver diseases. For patients with non-resectable HCC, treatment options include ablative and systemic therapies. However, the results are unsatisfactory with limited long-term survival. In the last few years there has been active research in the area of molecularly targeted agents for HCC including anti-angiogenic therapy, immunotherapy, antiviral therapy, and other agents targeting mammalian target of rapamycin (mTOR), and c-met among others. This chapter will look into current treatment options, discuss their advantages and disadvantages, as well as introduce new therapies that are under clinical investigation but not yet recommended by acceptable guidelines. Although there is tremendous research in progress, the treatment modalities offer limited survival benefit and thus the battle against HCC is far from over.

T Cells in Gastrointestinal Cancers: Role and Therapeutic Strategies

Conventional treatments of gastrointestinal cancers based on surgical resection and chemotherapy are not enough to eradicate potentially relapsing tumor cells and can also impair the immune system functions. Immunotherapies aim to help the body to eradicate cancer and other diseases, by modulating the immune system. They can be performed by active approaches, usually orchestrated by dendritic cell vaccines that present a specific tumor associated antigen to T cells, or passive approaches, which have the T cells as protagonist, and are based on antitumor antibodies, or adoptive cell transfer. T lymphocyte subsets can exhibit different role face to a tumor scenario, varying from an effective cellular antitumor response to a regulatory participation. Although a lot of protocols to combat cancer progression have been proposed, T cell-based immunotherapies in gastrointestinal cancers are still not approved for clinical applications mainly because of their side effects. Nowadays, promising protocols combining two or more approaches, aiming to create an efficient therapy without or with fewer side effects. In this chapter, we made a review about the role of T cells on cancer, especially focusing on gastrointestinal cancer immunotherapeutic methods.

The Role of Stem Cells in the Management of Hepatocellular Carcinoma

Despite the significant advances in the management of hepatocellular carcinoma (HCC), the results are still far from satisfactory. One of the reasons for this is the need to identify the mechanisms involved in the molecular pathogenesis of HCC, so as to be able to provide patient-targeted therapies. The difficulty in this endeavor lies in the multitude of pathways involved and the challenge of finding out how each one of them fits into the larger picture.

As is the case in several different organs, stem cells appear to have a critical role in the evolution of the liver and its neoplasms, as well as in key aspects of hepatic regeneration and response to various injury mechanisms. The goal of this chapter is to present basic principles of stem cells and identify pathways involved in the development of stem cells, which can at the same time affect the evolution and diagnosis of HCC. Finally, therapeutic strategies involving stem cells will be presented, in an effort to identify future challenges.