Igor Astsaturov, MD, PhD
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Fox Chase Cancer Center
333 Cottman Avenue
Philadelphia, PA 19111
Gastrointestinal cancers, Neuroendocrine carcinomas
Language(s) Other than English
I chose to stay at Fox Chase as an attending physician for the love of the institutional environment and the great patients I am so privileged to treat. I love my work for the great team spirit cultivated among my colleagues, physicians and nurses. I am extremely grateful to the fact that patients are at the center of everybody’s attention. It is easy for me to do my job in such an atmosphere of concern and indefatigable compassion.
Fox Chase also offers me an opportunity to work both in the clinic and in the lab, where I am studying cancer biology with the goal to design better treatment options for the patients. In my field of gastrointestinal malignancies, I am convinced that the treatment choices for each individual cancer patient will soon be defined by the molecular makeup of their cancer cells. This knowledge can help us match the treatment strategies with the biology of individual patient’s tumors. I am interested to translate the knowledge about cancer available in the lab to the clinic by conducting hypothesis-driven clinical trials.
I am deeply convinced that the best way to help our patients is to push the boundaries by doing clinical and basic research.
- Medical Oncology Fellow, Fox Chase Cancer Center, 2005-2008
- Internship and Residency in Internal Medicine, Good Samaritan Hospital, Baltimore, MD, 2002-2005
- Postdoctoral Research Fellow, Dept. of Immunology, University of Toronto, Ontario, Canada, 1998-2002
- Resident, Internal Medicine/Hematology, Russian Hematological Research Center, Moscow, Russia, 1992-1994
- MD, I.M.Sechenov Moscow Medical Academy, Moscow, 1992
- PhD, Russian Academy Research Center for Hematology, Moscow, 1997
- American Board of Internal Medicine
- Medical Oncology Certification
- Unrestricted Medical License MD427094, Pennsylvania State Medical Board
- Member, Laboratory Science Committee, Eastern Cooperative Oncology Group
- American Association for Cancer Research
- American Society of Clinical Oncology
- Ad hoc Junior Faculty member, NCI Esophago-Gastric Cancer Taskforce
Honors & Awards
- Training Award (ICRETT), International Union Against Cancer, Geneva, Switzerland
- Scholar-in-Training Award, AACR-OSI
- Sol Sherry Research Award, Temple University, Philadelphia, PA
- Fox Chase-Genentech Scholar, Fox Chase Cancer Center
In 2013, Melissa Kartasevich was enjoying life, raising her six year old daughter, Sarah and engaged to be married to her fiancé, Dennis Dupre. In April, she woke one morning with pain and discomfort on her left side. Assuming it was a result of sleeping in a bad position, she took pain medication and went to work. By lunch time, the pain worsened so Melissa went to the emergency room. The doctors ran some tests and performed a CAT scan, where they noticed her spleen had infracted, but didn't know the cause. Melissa was admitted to the hospital for five days, where she underwent further tests revealing a suspicious spot on her pancreas. Next, she had an endoscopic ultrasound (EUS) which confirmed the diagnosis. Melissa, 38, had pancreatic cancer. To say she was shocked would be an understatement.
In 2007 when Baha Malik started experiencing back pain, he ignored it. “You know – that macho thing we do,” shares the retired data specialist, who turned 78 in 2016. “Finally it got so excruciating that my wife demanded I go to a hospital. When I did that, a biopsy revealed that I had cancer of the pancreas. That’s when my primary physician made arrangements for me to go to Fox Chase Cancer Center – which was a real blessing.”
In September 2009, Barry Dixon was living and working in South Carolina with his fiancé and their son, Robert Phillip. As a maintenance technician for an apartment management firm, Barry performed a lot of physical labor. One day, while helping his cousin move, Barry thought he pulled something in his abdominal area. It caused more pain than he was used to. He went to the doctor on a Friday, who ordered further testing for the following Monday.
Cancer Metabolism and signaling
- The central role for sterol metabolism in regulation of cell growth and signaling
- Pancreatic cancer biology and "smart drugs" for treatment of pancreatic cancer
- Translating therapeutic concepts to the clinic using the platform of patient-derived avatar models and genetically engineered pancreatic cancer models
My lab opened in 2009 endowed with the challenge to define the critical regulators of tumor cell response to drugs targeting EGFR (Astsaturov, Science Signaling, 2010). From this initial task which ultimately led to 2 clinical trials in patients with head and neck and lung cancers, 3 NIH grants and 6 papers, we define a previously overlooked step of C4-demethylation in the enzymatic cascade of cholesterol biosynthesis. Inactivation of SC4MOL or NSDHL involved in the oxidative demethylation at C4 leads to dramatic alteration in the vesicular trafficking of the endocytosed EGFR and sensitizes cancer cells to EGFR inhibitors (Sukhanova, Cancer Discovery, 2013).
Following this initial lead, Linara Gabitova took on the challenge to pinpoint the mechanism executing such a dramatic effect of accumulating C4-methylated sterols. She found that LXR alpha was the critical effector triggered by these sterol species, so that activation of LXR can be used to deregulate cholesterol turnover in cancer synergistically with EGFR antagonists in in the KRAS-driven tumors (Cell Reports, 2015).
Our current interests are focused on pancreatic cancer where KRAS is the causative oncogenic mutation. We are looking for metabolic vulnerabilities in the cholesterol pathway as well as developing innovative drug delivery tools to improve lives of the patient with this devastating and thus far recalcitrant cancer.
Linara Gabitova, PhD
Diana Restifo, BS
Egor Bobrov, BS
Andrei Gorin, PhD
Anna Sukhanova, PhD
Eugenia Banina, MD
Gabitova L, Restifo D, Gorin A, Manocha K, Handorf E, Yang DH, Cai KQ, Klein-Szanto AJ, Cunningham D, Kratz LE, Herman GE, Golemis EA, Astsaturov I. Endogenous Sterol Metabolites Regulate Growth of EGFR/KRAS-Dependent Tumors via LXR. Cell Rep. 2015 Sep 22;12(11):1927-38. doi: 10.1016/j.celrep.2015.08.023. Epub 2015 Sep 3. PubMed; PubMed Central
Beeharry N, Banina E, Hittle J, Skobeleva N, Khazak V, Deacon S, Andrake M, Egleston BL, Peterson JR, Astsaturov I, Yen TJ. Re-purposing clinical kinase inhibitors to enhance chemosensitivity by overriding checkpoints. Cell Cycle.
2014;13(14):2172-91. doi: 10.4161/cc.29214. Epub 2014 Jun 23. PubMed; PubMed Central.
Perkins J, Boland P, Cohen SJ, Olszanski AJ, Zhou Y, Engstrom P, Astsaturov I. Successful imatinib therapy for neuroendocrine carcinoma with activating Kit mutation: a case study. J Natl Compr Canc Netw. 2014 Jun;12(6):847-52. PubMed; PubMed Central.
Gabitova L, Gorin A, Astsaturov I. Molecular pathways: sterols and receptor signaling in cancer. Clin Cancer Res. 2014 Jan 1;20(1):28-34. doi: 10.1158/1078-0432.CCR-13-0122. Epub 2013 Oct 24. Review. PubMed;PubMed Central.
Liu H, Xiao F, Serebriiskii IG, O'Brien SW, Maglaty MA, Astsaturov I, Litwin S, Martin LP, Proia DA, Golemis EA, Connolly DC. Network analysis identifies an HSP90-central hub susceptible in ovarian cancer. Clin Cancer Res. 2013 Sep 15;19(18):5053-67. doi: 10.1158/1078-0432.CCR-13-1115. Epub 2013 Jul 30. PubMed; PubMed Central.
Bagnyukova TV, Restifo D, Beeharry N, Gabitova L, Li T, Serebriiskii IG, Golemis EA, Astsaturov I. DUSP6 regulates drug sensitivity by modulating DNA damage response. Br J Cancer. 2013 Aug 20;109(4):1063-71. doi: 10.1038/bjc.2013.353. Epub 2013 Jul 9. PubMed; PubMed Central.
Sukhanova A, Gorin A, Serebriiskii IG, Gabitova L, Zheng H, Restifo D, Egleston BL, Cunningham D, Bagnyukova T, Liu H, Nikonova A, Adams GP, Zhou Y, Yang DH, Mehra R, Burtness B, Cai KQ, Klein-Szanto A, Kratz LE, Kelley RI, Weiner LM, Herman GE, Golemis EA, Astsaturov I. Targeting C4-demethylating genes in the cholesterol pathway sensitizes cancer cells to EGF receptor inhibitors via increased EGF receptor degradation. Cancer Discov. 2013 Jan;3(1):96-111. doi: 10.1158/2159-8290.CD-12-0031. Epub 2012 Nov 2. PubMed; PubMed Central.
Gorin A, Gabitova L, Astsaturov I. Regulation of cholesterol biosynthesis and cancer signaling. Curr Opin Pharmacol. 2012 Dec;12(6):710-6. doi: 10.1016/j.coph.2012.06.011. Epub 2012 Jul 21. Review. PubMed; PubMed Central.
Dotan E, Meropol NJ, Zhu F, Zambito F, Bove B, Cai KQ, Godwin AK, Golemis EA, Astsaturov I, Cohen SJ. Relationship of increased aurora kinase A gene copy number, prognosis and response to chemotherapy in patients with metastatic colorectal cancer. Br J Cancer. 2012 Feb 14;106(4):748-55. doi: 10.1038/bjc.2011.587. Epub 2012 Jan 12. PubMed; PubMed Central.
Bagnyukova TV, Serebriiskii IG, Zhou Y, Hopper-Borge EA, Golemis EA, Astsaturov I. Chemotherapy and signaling: How can targeted therapies supercharge cytotoxic agents? Cancer Biol Ther. 2010 Nov 1;10(9):839-53. Epub 2010 Nov 1. Review. PubMed; PubMed Central.