Augmentation of Nab -Paclitaxel Chemotherapy Response by Mechanistically Diverse Antiangiogenic Agents in Preclinical Gastric Cancer Models

Molecular Cancer Therapeutics
Niranjan AwasthiRoderich E Schwarz

Abstract

Gastric adenocarcinoma (GAC) remains the third most common cause of cancer-related deaths worldwide. Systemic chemotherapy is commonly recommended as a fundamental treatment for metastatic GAC; however, standard treatment has not been established yet. Angiogenesis plays a crucial role in the progression and metastasis of GAC. We evaluated therapeutic benefits of mechanistically diverse antiangiogenic agents in combination with nab-paclitaxel, a next-generation taxane, in preclinical models of GAC. Murine survival studies were performed in peritoneal dissemination models, whereas tumor growth studies were performed in subcutaneous GAC cell-derived or patient-derived xenografts. The mechanistic evaluation involved IHC and Immunoblot analysis in tumor samples. Nab-paclitaxel increased animal survival that was further improved by the addition of antiangiogenic agents ramucirumab (or its murine version DC101), cabozantinib and nintedanib. Nab-paclitaxel combination with nintedanib was most effective in improving animal survival, always greater than 300% over control. In cell-derived subcutaneous xenografts, nab-paclitaxel reduced tumor growth while all three antiangiogenic agents enhanced this effect, with nintedanib demonstrating t...Continue Reading

References

Jan 1, 1997·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·A WebbM Meehan
Dec 10, 1999·International Journal of Cancer. Journal International Du Cancer·J ItakuraM Korc
Oct 4, 2005·American Journal of Clinical Oncology·Sook Ryun ParkHark Kyun Kim
Jan 4, 2008·The New England Journal of Medicine·David CunninghamUNKNOWN Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom
Dec 17, 2008·Molecular Cancer Therapeutics·Jie Ma, David J Waxman
Oct 13, 2009·The Lancet Oncology·Narikazu BokuUNKNOWN Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group
Mar 12, 2011·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Yelena Y JanjigianManish A Shah
Aug 24, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jonathan A LedermannGordon Rustin
Sep 26, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Justin N Bottsford-MillerAnil K Sood
Jun 19, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Denise A Yardley
Sep 5, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Rossella EliseiSteven I Sherman
Sep 18, 2013·International Journal of Oncology·Chang-Ηua ZhangRoderich E Schwarz
Jan 1, 2011·Cancers·Yasuhiko KitadaiKei Shinagawa
Nov 23, 2013·Nature Reviews. Cancer·Hira Lal Goel, Arthur M Mercurio
Jul 25, 2015·Expert Review of Anticancer Therapy·John SyriosVassilis Georgoulias
Aug 2, 2015·Cancer Chemotherapy and Pharmacology·Nianhang ChenRajesh Chopra
Aug 6, 2015·Drug Design, Development and Therapy·Madappa N Kundranda, Jiaxin Niu
Dec 17, 2015·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Lindsey A TorreAhmedin Jemal
Dec 18, 2015·OncoTargets and Therapy·Niranjan Awasthi, Roderich E Schwarz
Aug 30, 2016·World Journal of Gastroenterology : WJG·Mitsuro Kanda, Yasuhiro Kodera
Mar 2, 2017·Current Oncology Reports·Nizar M TannirViktor Grünwald
Sep 13, 2017·Molecular and Clinical Oncology·Hironaga SatakeAkihito Tsuji

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