Gastrointestinal Cancers Symposium

GI 2017 Daily News - Friday

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Understanding Pancreatic Cancer Tumor Biology May Help Guide Future Treatments Dr. Volker Ellenrieder to discuss novel fi ndings and their translation to the clinic during keynote lecture D uring the last decade, there have been several important ad- vances in the molecular and biologic understanding of pan- creatic cancer. Volker Ellenrieder, MD, PhD, will discuss key novel fi ndings in the tumor biology of pancreatic cancer and how they might translate into the clinic during his keynote lec- ture, "The Promise of Biology in Advancing Early Diagnosis and Therapy" (January 20, 10:00 AM-11:00 AM). Dr. Ellenrieder is director of the Department of Gastroenterology and Gastrointestinal Oncology at the University Hospital of Göttin- ge n, Germany. He is also the head of the Göttinger Pancreatic Can- cer Program, an interdisciplinary platform combining translational research with molecular stratifi cation of patients with pancreatic cancer. Dr. Ellenrieder earned his medical degree at the University of Ulm, Germany. He earned his postdoctorate in the laboratory of Raul A. Urrutia, MD, at Mayo Clinic, Rochester, Minn. During his address, Dr. Ellenrieder will present recent and impor- tant fi ndings on epigenetics and genetics, intratumoral heterogene- ity, and the role of the tumor microenvironment, the desmoplastic stroma, and immune-editing phenotypes. He will extrapolate the potential of these novel fi ndings for future treatment strategies. Delving Into a Diffi cult Disease Dr. Ellenrieder has been researching pancreatic cancer tumor bi- ology for more than 15 years. His interest in the fi eld was sparked when the fi rst genetically modifi ed mouse models were reported, nicely recapitulating pancreatic carcinogenesis. "It became clear that oncogenic signaling and transcription fac- tors played major roles in the development and course of the dis- ease, and that infl ammation can drive these pathways," Dr. Ellenrieder said. Much of his early research in- volved TGF-ß signaling and its dual role in pancreatic carcino- genesis. "In early tumor stages, TGF- ß works as an important tumor suppressor, but in advanced stages, TGF-ß switches to a strong promoter of tumorigen- esis," Dr. Ellenrieder said. "TGF- ß then promotes migration and invasion, and these functions are associated with an epithelial to mesenchymal transdifferentiation process." In addition to TGF-ß, many other factors promote epithelial- mesenchymal transition features and eventually stimulate tumor cell invasion and metastasis in pancreatic cancer; among those are several transcription factors like NFATc1. 1 More recently, Dr. Ellenrieder's work has focused on the role of the NFAT family transcription factor in infl ammation-driven cancer. In 2014, Dr. Ellenrieder and colleagues published fi ndings showing that the transcription factors NFATc1 and STAT3 work cooperatively in pancreatic epithelial cells to promote KRAS G12D -driven carcino- genesis, and that this cooperativity occurs in pancreatitis-mediated Immune Checkpoint Inhibitors in Advanced Gastroesophageal Cancers Mariela Blum Murphy, MD, and Jaffer A. Ajani, MD C ure is not possible for most patients with lo- cally advanced gastro- esophageal cancers, and much progress remains to be made. Current strategies for localized disease include peri- operative chemotherapy and surgery 1 or surgery followed by adjunctive therapy with either chemotherapy 2 or chemoradia- tion. 3,4 However, after aggres- sive treatment, one-third of patients with locally advanced gastroesophageal cancers will develop metastatic disease. In patients with advanced disease, the median overall survival is approximately 9 months, and the 5-year survival rate is less than 4%. 5 Such patients are em- pirically treated with a combi- nation of a platinum agent and a fl uoropyrimidine, 6 with the addition of trastuzumab if the tumor expresses HER2/neu bio- markers. 7 After disease progression, op- tions for second-line treatment include taxanes, 8 ramucirumab (monotherapy or in combina- tion), 9,10 or single-agent irino- tecan, which provides a modest survival advantage versus best supportive care. 8,11 Among tar- geted agents, only trastuzum- ab 7 and ramucirumab 10 have yielded a statistically signifi cant survival advantage in a few pa- tients (ramucirumab resulted in a marginal advantage as a sin- gle agent, and the addition of trastuzumab led to only a mod- est advantage 12 ), and results from other targeted agents have been discouraging. 13,14 Harnessing the Immune System Fortunately, the paradigm is shifting to harness the power of the immune system. Under ordinary circumstances, most tumors evade the immune sys- tem, which is quite equipped to kill tumor cells. Thus, the tu- mor can thrive in the presence of a competent immune system. Uncovering the mechanisms of T-cell activation and its costim- ulatory signals 15 has provided the opportunity for new treat- ment avenues. The immune response is regulated by a fi ne balance between costimulatory and inhibitory signals. For ex- Attendee Tip of the Day View captured sessions and posters through Virtual Meeting. Virtual Meeting access is included in the registration fee. Presentations can be viewed via computer or mobile device or downloaded as a podcast. ➤ To access Virtual Meeting, visit the Attendee Resource Center (gicasym.org/arc). See Pancreatic Cancer Tumor Biology, Page 4 See Immune Checkpoint Inhibitors, Page 5 T A R G E T I N G C A N C E R C A R E Treatment of Short-Segment BE With High-Grade Dysplasia 4 My Meeting Experience: A Radiation Oncologist's Perspective 6 Highlights of GI-Related Articles From JOP 12 Refl ections F rom RESORCE 12 Pancreatic Cancer: Promising Therapies 16 Restaurant Recommendations 16 Symposium Essentials 17, 18, 21 ASTRO Releases Three New Patient Videos 17 Circulating Tumor Cells: How Close Are We? 18 Use SOSAP 2.0 to Prepare for Exams, Earn MOC/CME Credits 18 ASCO Launches JCO Clinical Cancer Informatics 21 Gastrointestinal Cancers in Chile 22 Join SSO 24 Using Big Data to Improve Clinical Research and Care 25 ASCO's Quality Training Program Shifts to Regional Settings 25 INSIDE Dr. Volker Ellenrieder See Left- and Right-Sided CRC, Page 3 DAILY NEWS FRIDAY · JA N UA RY 20 · SA N F RA N C I S CO Gastrointestinal Cancers Symposium O 2017 Left- and Right- Sided CRC: What Is the Impact on Clinical Decisions? Sebastian Stintzing, MD, and Volker Heinemann, MD, PhD R ecently, clinical data have demonstrated differences in prognosis for left- and right-sided primary tu- mors in colorectal cancer (CRC). Overall, patients with a primary tumor on the midgut, or right side of the colon (cecum, as- cending colon, hepatic fl exure, and transverse colon), have a signifi cantly shorter overall survival (OS) compared with patients with primary tumors on the hindgut, or left side of the colon (splenic fl exure, de- scending colon, sigmoid, and rectum). This has been shown for patients treated with che- motherapeutic agents alone,

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