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Article: HBI-8000, HUYABIO Lead Clinical Program, Is a Selective Histone Deacetylase Inhibitor With Therapeutic Benefits in Leukemia and in Solid Tumors.

Shojaei, Farbod / Goodenow, Bob / Lee, Gloria / Kabbinavar, Fairooz / Gillings, Mireille

2022 Volume 11, Page(s) 768685

Abstract: HBI-8000 is a small molecule inhibitor of class I HDACs and has been approved for the treatment of PTCL, ATL and, in combination with exemestane, in a subpopulation of breast cancer. Given the roles of HDACs in normal and cancerous cells, there are ... ...

Abstract	HBI-8000 is a small molecule inhibitor of class I HDACs and has been approved for the treatment of PTCL, ATL and, in combination with exemestane, in a subpopulation of breast cancer. Given the roles of HDACs in normal and cancerous cells, there are currently multiple clinical trials, by HUYABIO International, to test the efficacy of HBI-8000 in monotherapy or in combination settings in leukemias and in solid tumors. The current review is focused on the applications of HDACi HBI-8000 in cancer therapy and its potential in combination with DDR agents.
Language	English
Publishing date	2022-01-07
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2021.768685
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Article ; Online: Anti-angiogenesis therapy in cancer: current challenges and future perspectives.

Shojaei, Farbod

Cancer letters

2012 Volume 320, Issue 2, Page(s) 130–137

Abstract: It has been nearly 9years since the FDA (Food and Drug Administration) approved the first anti-angiogenic drug (bevacizumab) for treatment of metastatic colorectal cancer. Other angiogenic inhibitors have since been approved or are in different stages of ...

Abstract	It has been nearly 9years since the FDA (Food and Drug Administration) approved the first anti-angiogenic drug (bevacizumab) for treatment of metastatic colorectal cancer. Other angiogenic inhibitors have since been approved or are in different stages of clinical trials. However, continued clinical and preclinical investigations have identified major drawbacks associated with the application of this class of agents, including inherent/acquired resistance and induction of tumor invasiveness. In addition, lack of thoroughly validated predictive biomarkers has been one of the major hurdles to stratify cancer patients and to monitor tumor progression and response to the therapy. Investigations in clinic and preclinical models have provided some molecular and cellular mechanisms for the above challenges. This review aims to provide a concise update from recent findings.
MeSH term(s)	Angiogenesis Inhibitors/adverse effects ; Angiogenesis Inhibitors/therapeutic use ; Biomarkers, Tumor/metabolism ; Drug Resistance, Neoplasm ; Humans ; Neoplasm Metastasis ; Neoplasms/drug therapy ; Neoplasms/pathology ; Polymorphism, Single Nucleotide ; Stromal Cells/physiology ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Vascular Endothelial Growth Factor A/blood ; Vascular Endothelial Growth Factor A/genetics
Chemical Substances	Angiogenesis Inhibitors ; Biomarkers, Tumor ; Vascular Endothelial Growth Factor A
Language	English
Publishing date	2012-07-28
Publishing country	Ireland
Document type	Journal Article ; Review
ZDB-ID	195674-7
ISSN	1872-7980 ; 0304-3835
ISSN (online)	1872-7980
ISSN	0304-3835
DOI	10.1016/j.canlet.2012.03.008
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Article ; Online: The epigenetic immunomodulator, HBI-8000, enhances the response and reverses resistance to checkpoint inhibitors.

Bissonnette, Reid P / Cesario, Rosemary M / Goodenow, Bob / Shojaei, Farbod / Gillings, Mireille

BMC cancer

2021 Volume 21, Issue 1, Page(s) 969

Abstract: Background: Treatment with immune checkpoint inhibitors (ICIs) targeting CTLA-4 and the PD-1/PD-L1 axis is effective against many cancer types. However, due in part to unresponsiveness or acquired resistance, not all patients experience a durable ... ...

Abstract	Background: Treatment with immune checkpoint inhibitors (ICIs) targeting CTLA-4 and the PD-1/PD-L1 axis is effective against many cancer types. However, due in part to unresponsiveness or acquired resistance, not all patients experience a durable response to ICIs. HBI-8000 is a novel, orally bioavailable class I selective histone deacetylase inhibitor that directly modifies antitumor activity by inducing apoptosis, cell cycle arrest, and resensitization to apoptotic stimuli in adult T cell lymphoma patients. We hypothesized that HBI-8000 functions as an epigenetic immunomodulator to reprogram the tumor microenvironment from immunologically cold (nonresponsive) to hot (responsive). Method: Mice bearing syngeneic tumors (MC38 and CT26 murine colon carcinoma and A20 B-cell lymphoma were treated daily with HBI-8000 (orally), alone or in combination with PD-1, PD-1 L, or CTLA-4 antibodies. MC38 tumors were also analyzed in nanoString gene expression analysis. Results: HBI-8000 augmented the activity of ICI antibodies targeting either PD-1, PD-L1 or CTLA-4, and significantly increased tumor regression (p < 0.05) in the above models. Gene expression analysis of the treated MC38 tumors revealed significant changes in mRNA expression of immune checkpoints, with enhanced dendritic cell and antigen-presenting cell functions, and modulation of MHC class I and II molecules. Conclusions: These findings suggest that HBI-8000 mediates epigenetic modifications in the tumor microenvironment, leading to improved efficacy of ICIs, and provide strong rationale for combination therapies with ICIs and HBI-8000 in the clinical setting. Precis: As an HDACi, HBI-8000 plays an important role in priming the immune system in the tumor microenvironment. The current preclinical data further justifies testing combination of HBI-8000 and ICIs in the clinic.
MeSH term(s)	Animals ; Apoptosis ; Benzamides/pharmacology ; Cell Proliferation ; Colonic Neoplasms/drug therapy ; Colonic Neoplasms/immunology ; Colonic Neoplasms/metabolism ; Colonic Neoplasms/pathology ; Drug Resistance, Neoplasm/drug effects ; Epigenesis, Genetic ; Female ; Humans ; Immune Checkpoint Inhibitors/pharmacology ; Immunologic Factors/pharmacology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Nude ; Pyridines/pharmacology ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays
Chemical Substances	Benzamides ; HBI-8000 ; Immune Checkpoint Inhibitors ; Immunologic Factors ; Pyridines
Language	English
Publishing date	2021-08-30
Publishing country	England
Document type	Journal Article
ISSN	1471-2407
ISSN (online)	1471-2407
DOI	10.1186/s12885-021-08702-x
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Article: Anti-angiogenesis therapy in cancer: Current challenges and future perspectives

Shojaei, Farbod

Cancer letters. 2012 July 28, v. 320, no. 2

2012

Abstract	It has been nearly 9years since the FDA (Food and Drug Administration) approved the first anti-angiogenic drug (bevacizumab) for treatment of metastatic colorectal cancer. Other angiogenic inhibitors have since been approved or are in different stages of clinical trials. However, continued clinical and preclinical investigations have identified major drawbacks associated with the application of this class of agents, including inherent/acquired resistance and induction of tumor invasiveness. In addition, lack of thoroughly validated predictive biomarkers has been one of the major hurdles to stratify cancer patients and to monitor tumor progression and response to the therapy. Investigations in clinic and preclinical models have provided some molecular and cellular mechanisms for the above challenges. This review aims to provide a concise update from recent findings.
Keywords	Food and Drug Administration ; biomarkers ; clinical trials ; colorectal neoplasms ; drugs ; metastasis ; models ; patients ; therapeutics
Language	English
Dates of publication	2012-0728
Size	p. 130-137.
Publishing place	Elsevier Ireland Ltd
Document type	Article
ZDB-ID	195674-7
ISSN	1872-7980 ; 0304-3835
ISSN (online)	1872-7980
ISSN	0304-3835
DOI	10.1016/j.canlet.2012.03.008
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Smartwatch for the Detection of Atrial Fibrillation.

Tajrishi, Farbod Zahedi / Chitsazan, Mandana / Chitsazan, Mitra / Shojaei, Fahimehalsadat / Gunnam, Vamsikrishna / Chi, Gerald

Critical pathways in cardiology

2019 Volume 18, Issue 4, Page(s) 176–184

Abstract: Atrial fibrillation (AF) is the most common arrhythmia and poses a substantial economic burden due to associated thromboembolic complications. Screening for AF may theoretically be effective, but there is no consensus regarding the optimal screening ... ...

Abstract	Atrial fibrillation (AF) is the most common arrhythmia and poses a substantial economic burden due to associated thromboembolic complications. Screening for AF may theoretically be effective, but there is no consensus regarding the optimal screening method because the available tools are either invasive or not cost-effective. Recently, smartwatch industry has received a surge of interest for this purpose by introducing technologies such as photoplethysmography, artificial intelligence, and actual electrodes taking an electrocardiogram to measure and analyze heart rate and rhythm with relatively acceptable accuracy. Combined with other features such as ease of use and connectivity, smartwatches can potentially be used for large-scale AF screening and might eventually replace the current gold standards. In this review, we discuss the feasibility of this approach and summarize the current evidence on AF detection with smartwatches.
MeSH term(s)	Artificial Intelligence ; Atrial Fibrillation/diagnosis ; Electrocardiography ; Feasibility Studies ; Humans ; Mass Screening ; Photoplethysmography ; Wearable Electronic Devices
Language	English
Publishing date	2019-11-26
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2079676-6
ISSN	1535-2811 ; 1535-282X
ISSN (online)	1535-2811
ISSN	1535-282X
DOI	10.1097/HPC.0000000000000192
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Zs.A 5660: Show issues

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Article ; Online: Prognostic Value of Biomarkers in Cardiac Allograft Vasculopathy following Heart Transplantation: A Literature Review.

Habibi, Shaghayegh / Ghaffarpasand, Eiman / Shojaei, Fahimehalsadat / Alihashemi, Mahda / Kahe, Farima / Zahedi Tajrishi, Farbod / Chi, Gerald

Cardiology

2020 Volume 145, Issue 11, Page(s) 693–702

Abstract: Cardiac allograft vasculopathy (CAV), also known as cardiac transplant vasculopathy, is a major determinant of long-term survival among cardiac transplantation recipients. Histologically, CAV is featured by diffuse, concentric thickening of the vascular ... ...

Abstract	Cardiac allograft vasculopathy (CAV), also known as cardiac transplant vasculopathy, is a major determinant of long-term survival among cardiac transplantation recipients. Histologically, CAV is featured by diffuse, concentric thickening of the vascular wall, and primarily affects large and small epicardial coronary arteries, intramyocardial arteries, and veins. Owing to graft denervation, CAV typically follows an insidious course, and patients may not experience classic angina symptoms but instead present with progressive heart failure or ventricular arrhythmias. Recent studies on biomarkers have furthered the knowledge concerning the prediction and prognosis of CAV. Given its association with metabolic, thrombotic, inflammatory, and immunologic markers, CAV is likely to represent a complex multifactorial process that involves both immune-mediated and non-immune-mediated pathways. In order to identify the high-risk patients that would benefit from early intervention, future research is warranted to examine the usefulness of a biomarker panel in CAV risk stratification.
MeSH term(s)	Allografts ; Biomarkers ; Coronary Vessels ; Heart Transplantation/adverse effects ; Humans ; Prognosis
Chemical Substances	Biomarkers
Language	English
Publishing date	2020-09-04
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	80092-2
ISSN	1421-9751 ; 0008-6312
ISSN (online)	1421-9751
ISSN	0008-6312
DOI	10.1159/000509630
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Article ; Online: Refractoriness to antivascular endothelial growth factor treatment: role of myeloid cells.

Shojaei, Farbod / Ferrara, Napoleone

Cancer research

2008 Volume 68, Issue 14, Page(s) 5501–5504

Abstract: CD11b+Gr1+ cells, which include neutrophils, macrophages, and myeloid-derived suppressor cells, have been shown to contribute to tumor angiogenesis. Recently, we found that accumulation of CD11b+Gr1+ in tumors renders them refractory to angiogenic ... ...

Abstract	CD11b+Gr1+ cells, which include neutrophils, macrophages, and myeloid-derived suppressor cells, have been shown to contribute to tumor angiogenesis. Recently, we found that accumulation of CD11b+Gr1+ in tumors renders them refractory to angiogenic blockade by vascular endothelial growth factor (VEGF) antibodies. This effect was traced to a pathway of CD11b+Gr1+-mediated angiogenesis that is, at least in part, driven by the secreted protein Bv8, which is up-regulated by the important myeloid growth factor granulocyte colony-stimulating factor (G-CSF). Thus, G-CSF may promote tumor angiogenesis through a Bv8-dependent pathway that bypasses VEGF and renders tumors refractory to anti-VEGF therapy.
MeSH term(s)	Angiogenesis Inhibitors/pharmacology ; Animals ; Antigens, Neoplasm/chemistry ; CD11b Antigen/biosynthesis ; Gastrointestinal Hormones/biosynthesis ; Gene Expression Regulation, Neoplastic ; Granulocyte Colony-Stimulating Factor/metabolism ; Humans ; Models, Biological ; Myeloid Cells/cytology ; Myeloid Cells/metabolism ; Neovascularization, Pathologic ; Neuropeptides/biosynthesis ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Vascular Endothelial Growth Factor A/metabolism
Chemical Substances	Angiogenesis Inhibitors ; Antigens, Neoplasm ; CD11b Antigen ; Gastrointestinal Hormones ; Neuropeptides ; PROK2 protein, human ; Vascular Endothelial Growth Factor A ; Granulocyte Colony-Stimulating Factor (143011-72-7)
Language	English
Publishing date	2008-07-15
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-08-0925
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Article ; Online: Role of the microenvironment in tumor growth and in refractoriness/resistance to anti-angiogenic therapies.

Shojaei, Farbod / Ferrara, Napoleone

Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy

2008 Volume 11, Issue 6, Page(s) 219–230

Abstract: Angiogenesis is critical for growth of many tumor types and the development of anti-angiogenic agents opened a new era in cancer therapy. However, similar to other anti-cancer therapies, inherent/acquired resistance to anti-angiogenic drugs may occur in ... ...

Abstract	Angiogenesis is critical for growth of many tumor types and the development of anti-angiogenic agents opened a new era in cancer therapy. However, similar to other anti-cancer therapies, inherent/acquired resistance to anti-angiogenic drugs may occur in cancer patients leading to disease recurrence. Recent studies in several experimental models suggest that both tumor and non-tumor (stromal) cell types may be involved in the reduced responsiveness to the treatments. The current review focuses on the role of stromal cells in tumor growth and in refractoriness to anti-VEGF treatment.
MeSH term(s)	Angiogenesis Inhibitors/pharmacology ; Angiogenesis Inhibitors/therapeutic use ; Animals ; Drug Resistance, Neoplasm ; Humans ; Neoplasms/blood supply ; Neoplasms/drug therapy ; Neoplasms/immunology ; Neoplasms/metabolism ; Neoplasms/pathology ; Neovascularization, Pathologic/drug therapy ; Neovascularization, Pathologic/immunology ; Neovascularization, Pathologic/metabolism ; Vascular Endothelial Growth Factor A/antagonists & inhibitors
Chemical Substances	Angiogenesis Inhibitors ; Vascular Endothelial Growth Factor A
Language	English
Publishing date	2008-12
Publishing country	Scotland
Document type	Journal Article ; Review
ZDB-ID	1474513-6
ISSN	1532-2084 ; 1368-7646
ISSN (online)	1532-2084
ISSN	1368-7646
DOI	10.1016/j.drup.2008.09.001
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Zs.A 5099: Show issues

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Article: Molecular profiling of candidate human hematopoietic stem cells derived from human embryonic stem cells.

Shojaei, Farbod / Menendez, Pablo

Experimental hematology

2008 Volume 36, Issue 11, Page(s) 1436–1448

Abstract: Objective: Human embryonic stem cells (hESCs) have been differentiated into CD45(+) hematopoietic cells in vitro. A subset of hESC-derived CD45(+) cells coexpresses CD34 and show progenitor function in colony-forming units assays. These hESC-derived ... ...

Abstract	Objective: Human embryonic stem cells (hESCs) have been differentiated into CD45(+) hematopoietic cells in vitro. A subset of hESC-derived CD45(+) cells coexpresses CD34 and show progenitor function in colony-forming units assays. These hESC-derived hematopoietic stem (HSC), or progenitor cells, display, however, distinct functional properties, including poor repopulation ability; impaired differentiation; and lack of homing when compared to HSCs from fetal blood (FB) or cord blood. Whether these differences are cell-autonomous or driven by their microenvironment remains to be elucidated. Materials and methods: Here, to gain insight into the molecular determinants accounting for these functional differences, a gene-expression profiling comparing candidate hESC-HSCs vs FB-derived HSCs (FB-HSCs) was conducted. Results: Only 2.4% of differentially expressed transcripts were common for FB-HSCs and candidate hESC-HSCs, suggesting a completely different molecular signature for HSCs isolated from two different in utero ontogeny stages. Several key hematopoietic transcription factors, apoptosis and cycle regulators, and cell aggregation and homing genes may contribute to explain the functional differences between hESC-HSCs and FB-HSCs. Importantly, components of Notch and Wnt signaling pathways involved in HSC self-renewal and hematopoietic specification were significantly underexpressed in candidate hESC-HSCs. Conclusion: Our study provides a platform to understand the molecular basis underlying hESC-HSCs functional properties. Future studies are needed to address the functional role of the transcripts identified here, eventually leading to identification of intrinsic determinants and cytokines driving physiological specification of hESCs into definitive HSCs.
MeSH term(s)	Embryonic Stem Cells/cytology ; Gene Expression Profiling ; Hematopoietic Stem Cells/metabolism ; Humans ; Multigene Family ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/etiology
Language	English
Publishing date	2008-11
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	185107-x
ISSN	1873-2399 ; 0301-472X ; 0531-5573
ISSN (online)	1873-2399
ISSN	0301-472X ; 0531-5573
DOI	10.1016/j.exphem.2008.06.001
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Zs.A 922: Show issues

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Article: Antiangiogenic therapy for cancer: an update.

Shojaei, Farbod / Ferrara, Napoleone

Cancer journal (Sudbury, Mass.)

2007 Volume 13, Issue 6, Page(s) 345–348

Abstract: The identification and characterization of several important regulators of angiogenesis, which led to Food and Drug Administration approval of the first antiangiogenic drugs, has opened a new era in cancer therapy. This article focuses on the clinical ... ...

Abstract	The identification and characterization of several important regulators of angiogenesis, which led to Food and Drug Administration approval of the first antiangiogenic drugs, has opened a new era in cancer therapy. This article focuses on the clinical progress in targeting one of the major regulators of angiogenesis, vascular endothelial growth factor-A and also discusses some recent advances in the elucidation of potential cellular and molecular mechanisms underlying refractoriness or resistance to antiangiogenic therapies.
MeSH term(s)	Angiogenesis Inhibitors/therapeutic use ; Drug Approval ; Humans ; Neoplasms/blood supply ; Neoplasms/drug therapy ; Neovascularization, Pathologic/prevention & control ; United States ; United States Food and Drug Administration ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Vascular Endothelial Growth Factor A/genetics
Chemical Substances	Angiogenesis Inhibitors ; Vascular Endothelial Growth Factor A
Language	English
Publishing date	2007-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	2018400-1
ISSN	1528-9117 ; 1081-4442
ISSN	1528-9117 ; 1081-4442
DOI	10.1097/PPO.0b013e31815a7b69
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