Everolimus (RAD001) and anti-angiogenic cyclophosphamide show long-term control of gastric cancer growth in vivo

Cancer Biology & Therapy
Daniel CejkaVolker Wacheck

Abstract

Metronomic dosing of cytotoxic drugs such as cyclophosphamide has shown anti-angiogenic activity, most likely by inducing hypoxia in tumors. Hypoxia leads to activation of escape mechanisms allowing tumor cell survival. This potentially limits the activity of anti-angiogenic strategies. We hypothesized that mTORC1 inhibition by everolimus (RAD001) leads to suppression of HIF-1alpha and VEGF resulting in synergistic anti-tumor activity in combination with anti-angiogenically dosed cyclophosphamide. In vitro, effects of everolimus on mTORC1 signaling, proliferation, cell cycle, HIF-1alpha expression and VEGF secretion were evaluated in two gastric cancer cell lines. In vivo, anti-tumor activity of everolimus in combination with metronomic cyclophosphamide was studied in a NCI-N87 human gastric cancer SCID mouse xenograft model. Expression of Ki-67 and HIF-1alpha, activated caspase 3, microvascular density (MVD) and tumor necrotic area assessed. Everolimus decreased proliferation and attenuated production of HIF-1alpha as well as VEGF in gastric cancer cells in vitro. In vivo, everolimus significantly inhibited tumor growth. This anti-tumor activity was linked to a significant increase in tumor necrotic area (p < 0.02) and trends ...Continue Reading

Citations

Dec 1, 2011·Surgery Today·Takashi Oshima, Munetaka Masuda
Aug 28, 2009·Expert Reviews in Molecular Medicine·Evon PoonMargaret Ashcroft
Jul 26, 2011·Journal of Translational Medicine·Joanna D HolbrookRakesh Kumar
Mar 12, 2013·Cancer Chemotherapy and Pharmacology·Adriana RomitiPaolo Marchetti
Nov 7, 2014·Cancer Chemotherapy and Pharmacology·Caroline I PiatekAgustin A Garcia
Apr 14, 2009·Journal of Cancer Research and Clinical Oncology·Hendrik-Tobias Arkenau
Apr 20, 2012·Expert Opinion on Therapeutic Targets·Dylan T Jones, Adrian L Harris
Jun 25, 2009·Expert Opinion on Investigational Drugs·David P SamuelMark W Kieran
May 9, 2014·Expert Opinion on Investigational Drugs·Giuseppe AprileMario Scartozzi
Jan 24, 2013·Cancer Letters·Tetsuo NishiYasuhiro Kodera
Jan 22, 2010·Medical Hypotheses·Mark F McCartyFrancisco Contreras
Nov 21, 2009·Journal of the American Academy of Dermatology·Amy NguyenKristen M Kelly
Jul 6, 2015·Cancer Treatment Reviews·Chiara Alessandra CellaNicola Fazio
Sep 8, 2011·International Journal of Cancer. Journal International Du Cancer·Salah-Eddin Al-BatranAtsushi Ohtsu
Sep 11, 2012·Journal of Cellular Biochemistry·Yaozhong HuHe Huang
Mar 13, 2014·Journal of Surgical Oncology·Sun-Ju ByeonWoo Ho Kim
Oct 27, 2009·International Journal of Cancer. Journal International Du Cancer·Hideo ShigematsuMasakazu Fukushima
Dec 18, 2013·Biomarker Research·Miao-Zhen Qiu, Rui-Hua Xu
Feb 24, 2015·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Alexandra Thiel, Ari Ristimäki
Apr 12, 2013·The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi·Dae Young Cheung, Jae Kwang Kim
Dec 6, 2016·International Neurourology Journal·Phu TranSamuel J Klempner
Apr 13, 2011·Chemical Society Reviews·Ida Karin Nordgren, Ali Tavassoli
Mar 17, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Toshihiko DoiAtsushi Ohtsu
Oct 5, 2010·International Journal of Toxicology·Peter J BugelskiJacques Descotes
Aug 31, 2018·Expert Opinion on Pharmacotherapy·Roberto FilippiFrancesco Leone
May 17, 2018·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Yassine El HianiXian-Ping Dong
Jan 15, 2019·Current Pharmaceutical Design·Forouzan AmerizadehAfsane Bahrami
Oct 17, 2014·World Journal of Gastroenterology : WJG·Keishiro AoyagiKazuo Shirouzu
Jan 27, 2016·World Journal of Gastroenterology : WJG·Ozan YaziciSercan Aksoy
Jul 29, 2016·World Journal of Gastroenterology : WJG·Marwa MatboliOmar Abdel-Rahman
Feb 14, 2019·International Journal of Molecular Sciences·Tian TianJinhua Zhang
Nov 9, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yong ZhangAnpei Ye
Jun 30, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Thorsten FuerederVolker Wacheck
Mar 2, 2021·European Journal of Pharmacology·Ayda Baghery Saghchy KhorasaniDavood Bashash
Jun 9, 2021·DNA Repair·Romina Danesh PazhoohHamed Mirzaei
Aug 26, 2020·Current Cancer Drug Targets·Saba Hasan
Aug 8, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Geng-Ruei ChangYu-Chen Wang
Aug 28, 2021·Cancers·Rossella ReddavidMaurizio Degiuli

❮ Previous
Next ❯

Related Concepts

Related Feeds

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

Angiogenesis Inhibitors to Treat Cancer

Cancer treatments including angiogenesis inhibitors prevent tumor cells from receiving nutrients and oxygen. Here is the latest research on angiogenesis inhibitors for the treatment of cancer.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis