August 2020, Vol 1, No 1

Genomic alterations that are characteristic of intrahepatic cholangiocarcinoma (CCA) are well known. A study led by Jeffrey S. Ross, MD, Medical Director, Foundation Medicine, Cambridge, MA, examined whether genomic alterations from a primary tumor would differ from metastatic tumor tissue and liquid biopsy in patients with intrahepatic CCA. The study results were presented at the 2020 ASCO annual meeting.
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On June 2, 2020, the US Food and Drug Administration (FDA) granted an orphan drug designation to RenovoCath, an intra-arterial delivery device of gemcitabine (Gemzar) for the treatment of patients with cholangiocarcinoma (CCA). RenovoCath is developed by RenovoRx, a medical devices developer based in Los Altos, CA.
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One of the challenges that clinicians face when trying to diagnose cholangiocarcinoma (CCA) is obtaining enough tumor tissue to conduct molecular-profiling studies. A repeated biopsy could potentially be performed, but some tumors may be difficult or dangerous to reach to obtain the necessary tissue. As an alternative, blood testing for circulating tumor-cell DNA (ctDNA) can identify important molecular markers that could be missed if a repeated biopsy is difficult to perform.
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Analysis of next-generation sequencing has given physicians a depth of information regarding molecular aberrations beyond the capacity of traditional DNA sequencing technologies, but it has not led to breakthroughs in treatment and is not providing treatment recommendations for many patients. There is a need for better predictive assays to match the right drug with the right patient. At the 2020 American Association for Cancer Research annual meeting, Astrid Margossian, MD, PhD, Chief Medical Officer, SEngine Precision Medicine, Seattle, WA, presented results of a new assay designed to address this.
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Conventional antitumor therapies include chemotherapy, radiation, and surgery. After the identification of molecular aberrations as drivers for carcinogenesis, the introduction of therapies that target specific tumor-promoting pathways has revolutionized the development of cancer therapeutics.
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Mutations in the isocitrate dehydrogenase (IDH)1 and IDH2 enzymes are among the most common genetic alterations in intrahepatic cholangiocarcinoma (CCA) and are present in approximately 20% of patients. IDH proteins are enzymes involved in diverse cellular processes, including histone demethylation and DNA modification. The IDH2 protein is localized in the mitochondria and is a critical component of the tricarboxylic acid (also called citric acid or Krebs) cycle.
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The number of treatable tumor-specific molecular aberrations has grown substantially in the past decade, with a survival benefit obtained from matching biomarkers to therapies in several cancer types, such as breast, colon, and lung. Molecular diagnostic techniques have become fundamental in providing information about tumor diagnosis and prognosis as well as in driving therapeutic decisions in oncology practice.
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Cholangiocarcinoma (CCA), a group of heterogeneous cancers that originate in the bile ducts that connect the liver and gallbladder to the small intestine, affects 2000 to 3000 individuals annually in the United States. The disease most often affects older people aged ≥65 years and occurs slightly more frequently in men than in women.
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Rachna T. Shroff, MD, MS, Chief, Section of GI Medical Oncology, University of Arizona Cancer Center, Tucson, and Co-Chair of the 2020 Cholangiocarcinoma Foundation Annual Conference, provided an update of important global clinical trial developments since the last conference of the foundation. Dr Shroff reminded the audience that the ABC-02 clinical trial established the use of gemcitabine and cisplatin chemotherapy as the standard of care for patients with metastatic or unresectable cholangiocarcinoma (CCA) since 2010.
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During the 2020 Cholangiocarcinoma Foundation (CCF) Annual Conference, Melinda Bachini, Director of Advocacy for the foundation, presented an update on the foundation’s advocacy activities and initiatives toward promotion of the cholangiocarcinoma (CCA) community.
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