Header Information

NPRP11S-1214-170101
NPRP11S
Weill Cornell Medical College in Qatar
Award Active
01 Jun 2019
Prof. Dietrich Busselberg
4 Year(s)
13 Jul 2023
New
Anti-diabetic drugs in the treatment of breast cancer - identifying the molecular mechanism(s) and key biomarker(s)

Project Summary
Type 2 diabetes mellitus (hereafter termed as diabetes in the rest of the grant proposal unless specified otherwise) is one of the most common chronic disease worldwide and affects all types of societies including children, women, youth and adults (Hu FB, 2011). Evidence also links a higher incidence of cancer, in addition to the common diabetes associated complications (such as cardiovascular diseases, retinopathy, neuropathy, nephropathy and diabetic ketoacidosis), to diabetes (Glicksman AS et al., 1956; Glicksman AS & Rawson RW, 1956). Among the different forms of cancer, studies have reinforced a link between breast cancer risk and diabetes (Boyle P et al., 2012; Hardefeldt PJ et al., 2012). It was also reported that postmenopausal women 50 years or older who have diabetes have about a 20-27% increased risk of breast cancer (Boyle P et al., 2012). Subjects with breast cancer who also have diabetes have as much as a 50% increased chance of dying (mortality) from any cause (Peairs KS et al., 2011). Although several meta-analysis studies have supported the link between diabetes, incidence of breast cancer and mortality among breast cancer subjects the molecular mechanism(s) behind this link remains elusive. Among the different forms of breast cancer, triple-negative breast cancers (TNBC) do not benefit from hormonal or HER2 targeted therapies since they lack estrogen receptors (ER), progesterone receptors (PR) & HER2 (Bianchini G et al., 2016; Collignon J et al., 2016). Currently, alternative targeted therapies are lacking and chemotherapy remains the primary systemic treatment for patients with TNBC (Collignon J et al., 2016). Due to its aggressive nature, early recurrence, rapid metastasis & poor prognosis (Anders CK & Carey LA, 2009; Hudis CA & Gianni L, 2011), a major effort to identify potential molecular targets to treat patients who present with these kinds of tumors is underway. Recent research indicates that TNBCs may be more sensitive to platinum-based therapies (cisplatin, carboplatin) than other standard chemotherapeutic treatment regimens prompting a renewed interest in platinum-based chemotherapeutic agents as treatment for. Platinum based therapies, such as cisplatin, lead to double strand breaks & cross linking of double stranded DNA to cell induce death by inability to repair the damaged DNA (Yadav BS et al., 2014). However, subjects also develop chemo-resistance to such therapies (Li Z et al., 2017), hindering its success. Clearly, there is an unmet clinical requirement for novel &/or more efficient combinatory therapies. Additionally, there is little information linking the incidence of TNBC in diabetic subjects. The key innovation of our current grant proposal is that it links two first level priority themes, diabetes and cancer (breast cancer), within the Biomedical and Health Pillar of the Qatar National Research Strategy (QNRS). The broad scientific objective of the current proposal is to A) advance our understanding regarding the link between diabetes/hyperglycemia and breast cancer (specifically TNBCs) at the molecular level, B) establish the molecular mechanism(s), C) identify possible biomarker(s) of diagnostic and/or prognostic value and D) facilitate the discovery of new treatment regimens, which may include anti-diabetic/anti-cancer drug combinations. To this intend, using cellular and clinical studies the project team aims to: 1) Establish the effect of anti-diabetic drug pre-treatment or anti-diabetic drug combinatory (with anti-cancer drugs) therapies on breast cancer cells in relation to hyperglycemia/increased glucose levels. 2) Investigate whether hormone/chemotherapy resistant phenotypes of breast cancer (TNBCs) can be treated using the anti-diabetic drug or combinatory therapy. 3) Determine the molecular mechanism underlying the increased incidence of breast cancer (focusing more on TNBCs) in diabetic subjects and how the anti-diabetic drug or combinatory therapy alters/reverses these molecular changes in diabetes related breast cancer. 4) Identify molecular biomarker(s) that links diabetes and breast cancer (focusing more on TNBCs) and investigate whether anti-diabetic drug alone OR drug combinatory therapy related alteration in the biomarker may have prognostic value. 5) Link observations and inferences made from cellular (in vitro) studies to clinical subjects and study how they can be applicable among diabetic breast cancer subjects in Qatar. 6) Develop strategies and investigate whether the identified biomarker and its modulation using anti-diabetic drug OR combinatory therapies can address breast cancer in non-diabetics and other cancers (prostate, colorectal). The International Diabetes Federation (IDF), of which the State of Qatar is a member, estimates that there are 415 million people with diabetes in the world, more than 35.4 million of them in the Middle East and North Africa (MENA) region with 239,100 cases of diabetes in Qatar in 2015 with a prevalence of 13.5% among adults (IDF Diabetes Atlas - 8th Edition, 2017; IDF-MENA-Members-Qatar, 2017). In the State of Qatar, diabetes and cancer (especially breast cancer among women) contribute to a large portion of economic burden in the health sector. Additionally, in Qatar, breast cancer is diagnosed at a younger age and projections suggest newly diagnosed cases may increase by up to 60% in the future resulting in a major health concern for the nation. In 2015, breast cancer was the most common cause of cancer-related deaths (19%) amongst Qatari women (1466 cancer cases detected in Qatar in 2015: ministry, 2017). The successful completion of the project would thus create a strong impact in our understanding regarding the link between diabetes and breast cancer and facilitate the discovery of new treatment regimens, thus aiding in mitigation of disease progression and ultimately improving the quality of life among affected individuals in Qatar. (Please see research plan for references).
Diabetes; Breast Cancer; Efficacy of Drug Combinations; Apoptosis; Biomarkers
Applied research
3. Medical and Health Sciences
3.1 Basic Medicine
Pharmacology and Pharmacy
Yes
No
1. Natural Sciences
1.6 Biological Sciences
Cell Biology
No
Yes

Institution
Qatar University
Qatar
Collaborative Institution
Weill Cornell Medical College in Qatar
Qatar
Submitting Institution
Hamad Medical Corporation
Qatar
Collaborative Institution

Personnel
Lead PI
Prof. Dietrich Busselberg
Weill Cornell Medical College in Qatar
PI
Dr. Md Rahman
Qatar University
PI
Prof. Christopher Triggle
Weill Cornell Medical College in Qatar
PI
Dr. Salha Bujassoum AL Bader
Hamad Medical Corporation
Research Assistant
Mrs. Elizabeth Varghese
Weill Cornell Medical College in Qatar
Research Associate
Dr. Samson Mathews Samuel
Weill Cornell Medical College in Qatar

Outputs/Outcomes
Journal Paper
Anti‐Angiogenic Effects of Phytochemicals on miRNA Regulating Breast Cancer Progression
Elizabeth Varghese , Alena Liskova , Peter Kubatka , Samson Mathews Samuel and Dietrich Büsselberg
ISSN:2218273X
Journal Paper
Combination Therapy with Vitamin C Could Eradicate Cancer Stem Cells
Noothan Jyothi Satheesh, Samson Mathews Samuel and Dietrich Büsselberg
ISSN:2218273X
Journal Paper
Metformin: The Answer to Cancer in a Flower? Current Knowledge and Future Prospects of Metformin as an Anti-Cancer Agent in Breast Cancer
Samson Mathews Samuel , Elizabeth Varghese , Peter Kubatka , Chris R. Triggle and Dietrich Büsselberg
ISSN:2218273X
Journal Paper
Phytochemicals and Gastrointestinal Cancer: Cellular Mechanisms and Effects to Change Cancer Progression
Raghad Khalid AL-Ishaq , Anthony J. Overy and Dietrich Büsselberg
ISSN:2218273X
Journal Paper
Therapeutic Potential of Plant Phenolic Acids in the Treatment of Cancer
Mariam Abotaleb , Alena Liskova , Peter Kubatka and Dietrich Büsselberg
ISSN:2218273X
Journal Paper
Paclitaxel’s Mechanistic and Clinical Effects on Breast Cancer
Tala M. Abu Samaan , Marek Samec , Alena Liskova , Peter Kubatka and Dietrich Büsselberg
ISSN:2218273X
Online Paper
Metformin: The Answer to Cancer in a Flower? Current Knowledge and Future Prospects of Metformin as an Anti-Cancer Agent in Breast Cancer
Samson Mathews Samuel, Elizabeth Varghese, Peter Kubatka, Chris R. Triggle and Dietrich Büsselberg
DOI:10.3390/biom9120846
Online Paper
Combination Therapy with Vitamin C Could Eradicate Cancer Stem Cells
Noothan Jyothi Satheesh, Samson Mathews Samuel and Dietrich Büsselberg
DOI:10.3390/biom10010079
Online Paper
Anti-Angiogenic Effects of Phytochemicals on miRNA Regulating Breast Cancer Progression
Elizabeth Varghese, Alena Liskova, Peter Kubatka, Samson Mathews Samuel and Dietrich Büsselberg
DOI:10.3390/biom10020191
Online Paper
Therapeutic Potential of Plant Phenolic Acids in the Treatment of Cancer
Mariam Abotaleb, Alena Liskova, Peter Kubatka and Dietrich Büsselberg
DOI:10.3390/biom10020221
Online Paper
Phytochemicals and Gastrointestinal Cancer: Cellular Mechanisms and Effects to Change Cancer Progression
Raghad Khalid AL-Ishaq, Anthony J. Overy and Dietrich Büsselberg
DOI:10.3390/biom10010105
Online Paper
Paclitaxel’s Mechanistic and Clinical Effects on Breast Cancer
Tala M. Abu Samaan, Marek Samec, Alena Liskova, Peter Kubatka and Dietrich Büsselberg
DOI:10.3390/biom9120789
Journal Paper
Chemopreventive and Therapeutic Efficacy of Cinnamomum zeylanicum L. Bark in Experimental Breast Carcinoma: Mechanistic In Vivo and In Vitro Analyses
Peter Kubatka 1,2,* , Martin Kello 3 , Karol Kajo 4,5, Marek Samec 6, Karin Jasek 2, Desanka Vybohova 7, Sona Uramova 2, Alena Liskova 6, Vladimira Sadlonova 8, Lenka Koklesova 6, Radovan Murin 9 , Marian Adamkov 10, Karel Smejkal 11 , Emil Svajdlenka 11, Peter Solar 12 , Samson Mathews Samuel 13 , Monika Kassayova 14, Taeg Kyu Kwon 15 , Pavol Zubor 16, Martin Pec 1, Jan Danko 6, Dietrich Büsselberg 13,* and Jan Mojzis 3,*
ISSN:14203049
Online Paper
Chemopreventive and Therapeutic Efficacy of Cinnamomum zeylanicum L. Bark in Experimental Breast Carcinoma: Mechanistic In Vivo and In Vitro Analyses
Peter Kubatka, Martin Kello, Karol Kajo, Marek Samec, Karin Jasek, Desanka Vybohova, Sona Uramova, Alena Liskova, Vladimira Sadlonova, Lenka Koklesova, Radovan Murin, Marian Adamkov, Karel Smejkal, Emil Svajdlenka, Peter Solar, Samson Mathews Samuel, Monika Kassayova, Taeg Kyu Kwon, Pavol Zubor, Martin Pec, Jan Danko, Dietrich Büsselberg and Jan Mojzis
DOI:10.3390/molecules25061399
Journal Paper
Metformin: The Answer to Cancer in a Flower? Current Knowledge and Future Prospects of Metformin as an Anti-Cancer Agent in Breast Cancer.
Samson Mathews Samuel, Elizabeth Varghese, Peter Kubatka, Chris R. Triggle and Dietrich Büsselberg.
ISSN:2218273X
Journal Paper
Anti-Angiogenic Effects of Phytochemicals on miRNA Regulating Breast Cancer Progression.
Elizabeth Varghese, Alena Liskova, Peter Kubatka, Samson Mathews Samuel and Dietrich Büsselberg
ISSN:2218273X
Journal Paper
Therapeutic Potential of Plant Phenolic Acids in the Treatment of Cancer
Mariam Abotaleb, Alena Liskova, Peter Kubatka and Dietrich Büsselberg
ISSN:2218273X
Journal Paper
Phytochemicals and Gastrointestinal Cancer: Cellular Mechanisms and Effects to Change Cancer Progression
Raghad Khalid AL-Ishaq, Anthony J. Overy and Dietrich Büsselberg
ISSN:2218273X
Journal Paper
Combination Therapy with Vitamin C Could Eradicate Cancer Stem Cells
Noothan Jyothi Satheesh, Samson Mathews Samuel and Dietrich Büsselberg
ISSN:2218273X
Journal Paper
Paclitaxel’s Mechanistic and Clinical Effects on Breast Cancer
Tala M. Abu Samaan, Marek Samec, Alena Liskova, Peter Kubatka and Dietrich Büsselberg
ISSN:2218273X
Journal Paper
Flavonoids and Their Anti-Diabetic Effects: Cellular Mechanisms and Effects to Improve Blood Sugar Levels
Raghad Khalid AL-Ishaq, Mariam Abotaleb, Peter Kubatka, Karol Kajo and Dietrich Büsselberg
ISSN:2218273X
Journal Paper
Flavonoids in Cancer Metastasis
Alena Liskova , Lenka Koklesova , Marek Samec , Karel Smejkal ,Samson Mathews Samuel , Elizabeth Varghese , Mariam Abotaleb , Kamil Biringer ,Erik Kudela , Jan Danko , Mehdi Shakibaei , Taeg Kyu Kwon , Dietrich Büsselberg and Peter Kubatka
ISSN:20726694
Journal Paper
Targeting Glucose Metabolism to Overcome Resistance to Anticancer Chemotherapy in Breast Cancer
Elizabeth Varghese , Samson Mathews Samuel , Alena Líšková , Marek Samec ,Peter Kubatka and Dietrich Büsselberg
ISSN:20726694
Journal Paper
Counteracting Chemoresistance with Metformin in Breast Cancers: Targeting Cancer Stem Cells
Samson Mathews Samuel, Elizabeth Varghese, Lenka Koklesová, Alena Líšková, Peter Kubatka and Dietrich Büsselberg
ISSN:20726694
Journal Paper
Calcium Entry through TRPV1: A Potential Target for the Regulation of Proliferation and Apoptosis in Cancerous and Healthy Cells
Kevin Zhai , Alena Liskova , Peter Kubatka and Dietrich Büsselberg
ISSN:16616596
Journal Paper
Genoprotective activities of plant natural substances in cancer and chemopreventive strategies in the context of 3P medicine
Lenka Koklesova, Alena Liskova, Marek Samec, Tawar Qaradakhi, Anthony Zulli,Karel Smejkal, Karol Kajo, Jana Jakubikova, Payam Behzadi, Martin Pec, Pavol Zubor, Kamil Biringer Taeg Kyu Kwon, Dietrich Büsselberg, Gustavo R. Sarria, Frank A. Giordano, Olga Golubnitschaja,Peter Kubatka
ISSN:18785085
Journal Paper
Carotenoids in Cancer Apoptosis—The Road from Bench to Bedside and Back
Lenka Koklesova, Alena Liskova, Marek Samec, Constanze Buhrmann , Samson Mathews Samuel , Elizabeth Varghese, Milad Ashrafizadeh , Masoud Najafi, Mehdi Shakibaei , Dietrich Büsselberg , Frank A. Giordano, Olga Golubnitschaja and Peter Kubatka
ISSN:20726694
Journal Paper
Curcumin’s Beneficial Effects on Neuroblastoma: Mechanisms, Challenges, and Potential Solutions
Kevin Zhai , Aranka Brockmüller , Peter Kubatka , Mehdi Shakibaei and Dietrich Büsselberg
ISSN:2218273X
Journal Paper
Carotenoids in Cancer Metastasis—Status Quo and Outlook
Lenka Koklesova , Alena Liskova , Marek Samec , Kevin Zhai , Mariam Abotaleb , Milad Ashrafizadeh , Aranka Brockmueller , Mehdi Shakibaei , Kamil Biringer , Ondrej Bugos , Masoud Najafi , Olga Golubnitschaja , Dietrich Büsselberg and Peter Kubatka
ISSN:2218273X
Journal Paper
Rhus coriaria L. (Sumac) Demonstrates Oncostatic Activity in the Therapeutic and Preventive Model of Breast Carcinoma
Peter Kubatka, Martin Kello, Karol Kajo, Marek Samec, Alena Liskova, Karin Jasek,Lenka Koklesova , Tomas Kuruc , Marian Adamkov , Karel Smejkal , Emil Svajdlenka , Peter Solar ,Martin Pec , Dietrich Büsselberg , Vladimira Sadlonova and Jan Mojzis
ISSN:14220067
Journal Paper
Bacteriophage Treatment: Critical Evaluation of Its Application on World Health Organization Priority Pathogens
Raghad Khalid AL‐Ishaq, Sini Skariah and Dietrich Büsselberg
ISSN:19994915
Journal Paper
Flavonoids Targeting HIF-1, Implications on Cancer Metabolism
Marek Samec , Alena Liskova , Lenka Koklesova , Sandra Mersakova , Jan Strnadel , Karol Kajo , Martin Pec , Kevin Zhai , Karel Smejkal , Sepideh Mirzaei , Kiavash Hushmandi , Milad Ashrafizadeh Luciano Saso , Aranka Brockmueller , Mehdi Shakibaei , Dietrich Büsselberg and Peter Kubatka
ISSN:20726694
Journal Paper
Resveratrol’s Anti-Cancer Effects through the Modulation of Tumor Glucose Metabolism
Aranka Brockmueller, Saba Sameri, Alena Liskova, Kevin Zhai, Elizabeth Varghese , Samson Mathews Samuel, Dietrich Büsselberg, Peter Kubatka and Mehdi Shakibaei
ISSN:20726694
Journal Paper
Flavonoids against the SARS-CoV-2 induced inflammatory storm
Alena Liskova , Marek Samec , Lenka Koklesova , Samson M. Samuel , Kevin Zhai ,Raghad Khalid Al-Ishaq , Mariam Abotaleb , Vladimir Nosal , Karol Kajo ,Milad Ashrafizadeh , Ali Zarrabi , Aranka Brockmueller , Mehdi Shakibaei , Peter Sabaka ,Ioana Mozosj, , David Ullrich , Robert Prosecky m, Giampiero La Rocca , Martin Caprnda ,Dietrich Büsselberg , Luis Rodrigo , Peter Kruzliak , Peter Kubatka
ISSN:07533322
Journal Paper
Mitochondrial impairments in aetiopathology of multifactorial diseases: common origin but individual outcomes in context of 3P medicine
Lenka Koklesova, Marek Samec, Alena Liskova, Kevin Zhai, Dietrich Büsselberg, Frank A. Giordano, Peter Kubatka, Olga Golunitschaja
ISSN:18785085
Journal Paper
Flavonoids Alleviate Peripheral Neuropathy Induced by Anticancer Drugs
Manaal Siddiqui , Basma Abdellatif , Kevin Zhai Alena Liskova , Peter Kubatka and Dietrich Büsselberg
ISSN:20726694
Journal Paper
Flavonoids against the Warburg phenotype—concepts of predictive, preventive and personalised medicine to cut the Gordian knot of cancer cell metabolism
Marek Samec, Alena Liskova, Lenka Koklesova, Samson Mathews Samuel, Kevin Zhai, Constanze Buhrmann, Elizabeth Varghese, Mariam Abotaleb, Tawar Qaradakhi, Anthony Zulli, Martin Kello, Jan Mojzis, Pavol Zubor, Taeg Kyu Kwon, Mehdi Shakibaei, Dietrich Büsselberg, Gustavo R. Sarria, Olga Golubnitschaja & Peter Kubatka
ISSN:18785085
Journal Paper
Bacteriophage Treatment: Critical Evaluation of Its Application on World Health Organization Priority Pathogens
Raghad Khalid AL‐Ishaq, Sini Skariah and Dietrich Büsselberg
ISSN:19994915
Journal Paper
Mitochondrial impairments in aetiopathology of multifactorial diseases: common origin but individual outcomes in context of 3P medicine.
Lenka Koklesova, Marek Samec, Alena Liskova, Kevin Zhai, Dietrich Büsselberg, Frank A. Giordano, Peter Kubatka, Olga Golunitschaja
ISSN:18785085
Journal Paper
Calcium Entry through TRPV1: A Potential Target for the Regulation of Proliferation and Apoptosis in Cancerous and Healthy Cells
Kevin Zhai , Alena Liskova , Peter Kubatka and Dietrich Büsselberg
ISSN:14220067
Journal Paper
Genoprotective activities of plant natural substances in cancer and chemopreventive strategies in the context of 3P medicine
Lenka Koklesova, Alena Liskova, Marek Samec, Tawar Qaradakhi, Anthony Zulli,Karel Smejkal, Karol Kajo, Jana Jakubikova, Payam Behzadi, Martin Pec, Pavol Zubor, Kamil Biringer Taeg Kyu Kwon, Dietrich Büsselberg, Gustavo R. Sarria, Frank A. Giordano, Olga Golubnitschaja,Peter Kubatka
ISSN:14220067