This Fox Chase professor participates in the Undergraduate Summer Research Fellowship.
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Igor Astsaturov, MD, PhD
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- Clinical Locations
- About
- Education and Training
- Patient Stories
- Research Profile
- Lab Staff
- Publications
Clinical Locations
Primary Location
Fox Chase Cancer Center
333 Cottman Avenue
Philadelphia, PA 19111
About
Associate Professor, Department of Hematology/Oncology
Co-Director, Marvin & Concetta Greenberg Pancreatic Cancer Institute
Specialties
Treatment Focus
Gastrointestinal cancers, Neuroendocrine carcinomas
Research Program
Language(s) Other than English
Russian
Treatment Philosophy
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.
Education and Training
Educational Background
- Fellow, Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, 2005-2008
- Intern and Resident, Internal Medicine, Good Samaritan Hospital, Baltimore, MD, 2002-2005
- Postdoctoral Research Fellow, 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
Certifications
- American Board of Internal Medicine
- Medical Oncology Certification
- Unrestricted Medical License MD427094, Pennsylvania State Medical Board
Memberships
- 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
Patient Stories
Nick Pifani
Pancreatic Cancer
Nick Pifani
Pancreatic Cancer
I’m 45 and live in Delran, New Jersey, with my wife and two kids. I work as a vice president of business development for MasterCard, and in my spare time I love to run.
I’ve run marathons and completed an Ironman 70.3 (also known as a Half Ironman), which consists of a 1.2-mile swim, a 56-mile bike ride, and a 13.1-mile run. So, I’m no stranger to pain and discomfort.
Andre Burke
Pancreatic Cancer
Andre Burke
Pancreatic Cancer
I often share my story and always encourage people who feel something is wrong to go to the doctor to get checked out. If you wait too long, it may be too late. I am thankful that I took that advice.
Barry Dixon
Neuroendocrine Tumors
Barry Dixon
Neuroendocrine Tumors
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.
Research Profile
Research Program
Research Interests
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
Lab Overview
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 et al., 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).
Dr. Gabitova-Cornell next developed a mouse model of pancreatic cancer to study the role of mevalonate pathway in pancreatic carcinogenesis (Cancer Cell, 2020). She discovered a mechanism by which cholesterol metabolism controls the development and differentiation of pancreatic ductal adenocarcinoma (PDAC). In her novel mouse model, disruption of distal cholesterol biosynthesis by conditional inactivation of the rate limiting enzyme Nsdhl, or treatment with cholesterol-lowering statins switches glandular pancreatic carcinomas to a basal (mesenchymal) phenotype in mouse models driven by KrasG12D expression and homozygous Trp53 loss. Consistently, PDACs in patients receiving statins show enhanced mesenchymal features. Mechanistically, statins and NSDHL loss induce SREBP1 activation, which promotes the expression of Tgfb1 enabling epithelial-mesenchymal transition. Evidence from patient samples in this study suggests activation of TGFβ signaling and epithelial-mesenchymal transition by cholesterol-lowering statins may promote basal type of PDAC conferring poor outcomes in patients.
In an ongoing productive collaboration with a partnering laboratory of Dr. Edna Cukierman, we have begun in-depth analyses of the role cancer-associated fibroblasts (CAFs) in pancreatic cancer. We are currently investigating the role of CAFs in providing tumor cells with essential lipids such as cholesterol and other membrane lipid particles. This project led by a postdoctoral fellow, Dr. Charline Ogier, is aimed to develop new strategies to disrupt CAF-cancer cell interactions. 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.
Former Staff
Linara Gabitova-Cortnell, PhD
Andrei Gorin, PhD
Anna Sukhanova, PhD
Eugenia Banina, MD
Lab Staff
Publications
Selected Publications
Gabitova-Cornell, L., Surumbayeva, A., Peri, S, Franco-Barraza, J, Restifo, D, Weitz, N, Ogier, C, Goldman, AR, Hartman, TR, Francescone, R, Tan, YF, Nicolas, E, Shah, N, Handorf, EA, Cai, QK, O’Reilly, AM, Sloma, I, Chiaverelli, R, Moffitt, RA, Khazak, V, Fang, CY, Golemis, EA, Cukierman, E, Astsaturov, I. Cholesterol pathway inhibition induces TGFβ signaling to promote basal differentiation in pancreatic cancer. Cancer Cell. 2020,38(4):p.567-583e11.PMID: 32976774; PMCID: PMC7572882; doi.org/10.1016/j.ccell.2020.08.015. –cover feature article, Editorial Preview; highlighted-Science Signaling, 10 Nov 2020: Vol. 13, Issue 657, DOI: 10.1126/scisignal.abf5642
Francescone, R., Barbosa Vendramini-Costa, D., Franco-Barraza, J., Wagner, J., Muir, A., Lau, A. N., Gabitova, L., Pazina, T., Gupta, S., Luong, T., Rollins, D., Malik, R., Thapa, R. J., Restifo, D., Zhou, Y., Cai, K. Q., Hensley, H. H., Tan, Y., Kruger, W. D., Devarajan, K., Balachandran, S., Klein-Szanto, A. J., Wang, H., El-Deiry, W. S., Vander Heiden, M. G., Peri, S., Campbell, K. S., Astsaturov, I.,Cukierman, E. Cancer Discovery 2020. PubMed PMID: 33127842; PubMed Central PMCID: pending. DOI: 10.1158/2159-8290.CD-20-0775
Sahai E, Astsaturov I, Cukierman E, DeNardo DG, Egeblad M, Evans RM, Fearon D, Greten FR, Hingorani SR, Hunter T, Hynes RO, Jain RK, Janowitz T, Jorgensen C, Kimmelman AC, Kolonin MG, Maki RG, Powers RS, Puré E, Ramirez DC, Scherz-Shouval R, Sherman MH, Stewart S, Tlsty TD, Tuveson DA, Watt FM, Weaver V, Weeraratna AT, Werb Z. A framework for advancing our understanding of cancer-associated fibroblasts. Nat Rev Cancer. 2020 Jan 24;PubMed PMID: 31980749.
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
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.
Additional Publications
Clinical Locations
Primary Location
Fox Chase Cancer Center
333 Cottman Avenue
Philadelphia, PA 19111
Associate Professor, Department of Hematology/Oncology
Co-Director, Marvin & Concetta Greenberg Pancreatic Cancer Institute
Treatment Focus
Gastrointestinal cancers, Neuroendocrine carcinomas
Research Program
Language(s) Other than English
Russian
Treatment Philosophy
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.
Education
Educational Background
- Fellow, Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, 2005-2008
- Intern and Resident, Internal Medicine, Good Samaritan Hospital, Baltimore, MD, 2002-2005
- Postdoctoral Research Fellow, 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
Certifications
- American Board of Internal Medicine
- Medical Oncology Certification
- Unrestricted Medical License MD427094, Pennsylvania State Medical Board
Memberships
- 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
Research Profile
Research Interests
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
Lab Overview
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 et al., 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).
Dr. Gabitova-Cornell next developed a mouse model of pancreatic cancer to study the role of mevalonate pathway in pancreatic carcinogenesis (Cancer Cell, 2020). She discovered a mechanism by which cholesterol metabolism controls the development and differentiation of pancreatic ductal adenocarcinoma (PDAC). In her novel mouse model, disruption of distal cholesterol biosynthesis by conditional inactivation of the rate limiting enzyme Nsdhl, or treatment with cholesterol-lowering statins switches glandular pancreatic carcinomas to a basal (mesenchymal) phenotype in mouse models driven by KrasG12D expression and homozygous Trp53 loss. Consistently, PDACs in patients receiving statins show enhanced mesenchymal features. Mechanistically, statins and NSDHL loss induce SREBP1 activation, which promotes the expression of Tgfb1 enabling epithelial-mesenchymal transition. Evidence from patient samples in this study suggests activation of TGFβ signaling and epithelial-mesenchymal transition by cholesterol-lowering statins may promote basal type of PDAC conferring poor outcomes in patients.
In an ongoing productive collaboration with a partnering laboratory of Dr. Edna Cukierman, we have begun in-depth analyses of the role cancer-associated fibroblasts (CAFs) in pancreatic cancer. We are currently investigating the role of CAFs in providing tumor cells with essential lipids such as cholesterol and other membrane lipid particles. This project led by a postdoctoral fellow, Dr. Charline Ogier, is aimed to develop new strategies to disrupt CAF-cancer cell interactions. 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.
Former Staff
Linara Gabitova-Cortnell, PhD
Andrei Gorin, PhD
Anna Sukhanova, PhD
Eugenia Banina, MD
Lab Staff
Publications
Selected Publications
Gabitova-Cornell, L., Surumbayeva, A., Peri, S, Franco-Barraza, J, Restifo, D, Weitz, N, Ogier, C, Goldman, AR, Hartman, TR, Francescone, R, Tan, YF, Nicolas, E, Shah, N, Handorf, EA, Cai, QK, O’Reilly, AM, Sloma, I, Chiaverelli, R, Moffitt, RA, Khazak, V, Fang, CY, Golemis, EA, Cukierman, E, Astsaturov, I. Cholesterol pathway inhibition induces TGFβ signaling to promote basal differentiation in pancreatic cancer. Cancer Cell. 2020,38(4):p.567-583e11.PMID: 32976774; PMCID: PMC7572882; doi.org/10.1016/j.ccell.2020.08.015. –cover feature article, Editorial Preview; highlighted-Science Signaling, 10 Nov 2020: Vol. 13, Issue 657, DOI: 10.1126/scisignal.abf5642
Francescone, R., Barbosa Vendramini-Costa, D., Franco-Barraza, J., Wagner, J., Muir, A., Lau, A. N., Gabitova, L., Pazina, T., Gupta, S., Luong, T., Rollins, D., Malik, R., Thapa, R. J., Restifo, D., Zhou, Y., Cai, K. Q., Hensley, H. H., Tan, Y., Kruger, W. D., Devarajan, K., Balachandran, S., Klein-Szanto, A. J., Wang, H., El-Deiry, W. S., Vander Heiden, M. G., Peri, S., Campbell, K. S., Astsaturov, I.,Cukierman, E. Cancer Discovery 2020. PubMed PMID: 33127842; PubMed Central PMCID: pending. DOI: 10.1158/2159-8290.CD-20-0775
Sahai E, Astsaturov I, Cukierman E, DeNardo DG, Egeblad M, Evans RM, Fearon D, Greten FR, Hingorani SR, Hunter T, Hynes RO, Jain RK, Janowitz T, Jorgensen C, Kimmelman AC, Kolonin MG, Maki RG, Powers RS, Puré E, Ramirez DC, Scherz-Shouval R, Sherman MH, Stewart S, Tlsty TD, Tuveson DA, Watt FM, Weaver V, Weeraratna AT, Werb Z. A framework for advancing our understanding of cancer-associated fibroblasts. Nat Rev Cancer. 2020 Jan 24;PubMed PMID: 31980749.
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
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.
Additional Publications
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