Donatella Marino

Biliary tract carcinomas: From chemotherapy to targeted therapy

Biliary tract carcinomas (BTC) are a group of tumours arising from the epithelial cells of intra- and extra-hepatic biliaryducts and the gallbladder, characterised by a poor prognosis. Surgery is the only curative procedure, but the risk of recurrence is high and furthermore, the majority of patients present with unresectable disease at the time of diagnosis. Systemic therapy is the mainstay of treatment for patients who present recurrent or metastatic disease. Progress has been made in the last decade to identify the most effective chemotherapy regimens, with the recent recommendation of the combination of gemcitabine-cisplatin as the standard schedule. Comprehension of the molecular basis of cholangiocarcinogenesis and tumour progression has recently led to the experimentation of targeted therapies in patients with BTC, demonstrating promising results. In this review we will discuss the clinical experience with systemic treatment for BTC, focusing on future directions with targeted therapies.

Panitumumab in combination with gemcitabine and oxaliplatin does not prolong survival in wild‐type KRAS advanced biliary tract cancer: A randomized phase 2 trial (Vecti‐BIL study)

Biliary tract cancer (BTC) is a rare and lethal disease with few therapeutic options. Preclinical data suggest that the epidermal growth factor receptor (EGFR) pathway could be involved in its progression.

Panitumumab in combination with infusional oxaliplatin and oral capecitabine for conversion therapy in patients with colon cancer and advanced liver metastases. The MetaPan study.

Preoperative chemotherapy improves the outcome in patients with colorectal cancer with liver metastases. In the current study, the authors evaluated the activity of a conversion treatment with the combination of capecitabine plus oxaliplatin (XELOX) used in association with panitumumab in patients with unresectable, liver‐only, metastatic colon cancer.

Fluoropyrimidine-induced cardiotoxicity

Fluoropyrimidines (5-fluorouracil and capecitabine) are antimetabolite drugs, widely used for the treatment of a variety of cancers, both in adjuvant and in metastatic setting. Although the most common toxicities of these drugs have been extensively studied, robust data and comprehensive characterization still lack concerning fluoropyrimidine-induced cardiotoxicity (FIC), an infrequent but potentially life-threatening toxicity. This review summarizes the current state of knowledge of FIC with special regard to proposed pathogenetic models (coronary vasospasm, endothelium and cardiomyocytes damage, toxic metabolites, dihydropyrimidine dehydrogenase deficiency); risk and predictive factors; efficacy and usefulness in detection of laboratory markers, electrocardiographic changes and cardiac imaging; and specific treatment, including a novel agent, uridine triacetate. The role of alternative chemotherapeutic options, namely raltitrexed and TAS-102, is discussed, and, lastly, we overview the most promising future directions in the research on FIC and development of diagnostic tools, including microRNA technology.

The Immune Revolution in Gastrointestinal Tumours: Leading the Way or Just Following?

AbstractThe encouraging results in immunotherapy for melanoma also led the way for translational and clinical research about immune-related mechanisms possibly relevant for gastrointestinal tumours. It is in fact now evident that the immune checkpoint modulation and in particular cell-mediated immune-response through programmed cell death-1 (PD-1) and the cytotoxic T-lymphocyte antigen-4 (CTLA4) receptors along with the regulatory T cells activity all have a relevant role in gastrointestinal cancers as well. This review aims to explore the state of the art of immunotherapy for gastrointestinal tumours, deepening recent scientific evidence regarding anti PD-1/PDL-1 and anti CTLA4 monoclonal antibodies, peptide based vaccine, DNA based vaccine, and pulsed dendritic cells, either alone or in combination with other antineoplastic medical therapy and locoregional treatments. Considering the non-negligible toxicity profile deriving from such a treatment approach, predictive biomarkers of response to immunotherapy in gastrointestinal cancer are also urgently needed in order to better select the patients’ group with the highest likelihood of benefit.

Tracking the 2015 gastrointestinal cancers symposium: Bridging cancer biology to clinical gastrointestinal oncology

The 2015 Gastrointestinal Cancers Symposium (San Francisco, CA, USA; January 15–17) is the world-class conference co-sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, the American Gastroenterological Association Institute, and the Society of Surgical Oncology, in which the most innovative research results in digestive tract oncology are presented and discussed. In its twelfth edition, the meeting has provided new insights focusing on the underpinning biology and clinical management of gastrointestinal malignancies. More than 3,400 health care professionals gathered from all over the world to share their experiences on how to bridge the recent novelties in cancer biology with everyday medical practice. In this article, the authors report on the most significant advances, didactically moving on three different anatomic tracks: gastroesophageal malignancies, pancreatic and biliary cancers, and colorectal adenocarcinomas.

Targeted agents: how can we improve the outcome in biliary tract cancer?

The management of biliary tract cancer (BTC) has deeply changed in the past decade. Just few years ago patients with advanced disease had no effective treatment options but supportive therapy. Palliative chemotherapy was often administered in the absence of evidence of efficacy, as no randomized studies were available.

Emerging molecular target antagonists for the treatment of biliary tract cancer

ABSTRACT Introduction: Biliary tract cancers (BTCs) are a heterogeneous group of cancers, characterized by low incidence but poor prognosis. Even after complete surgical resection for early stage, relapse is frequent and the lack of effective treatments contributes to the dismal prognosis. To date, the only standard treatment in first-line is cisplatin/gemcitabine combination, whereas no standard in 2nd-line has been defined. Hence, the current goal is to better understand the biology of BTCs, discovering new treatment methods and improving clinical outcomes. Areas covered: The development of next-generation-sequencing has unveiled the picture of the molecular signatures characterizing BTCs, leading to the identification of actionable mutations in biomarker-driven clinical trials. In this review we will cover the genetic landscape of BTC, focusing on the efficacy of existing treatments. Furthermore, we will discuss emerging molecular targets and evaluate the findings of pre-clinical studies. Finally, the encouraging results of clinical trials involving targeted therapies or immunotherapy will be reviewed. Expert opinion: FGFR fusion rearrangements and IDH1 or IDH2 mutations are the most promising targeted treatments under evaluation. In addition, innovative trial design will allow to offer a chance for tailored medicine to infrequent subgroups of BTCs patients based on their molecular features rather than their histology.