Special Issue "Chemotherapeutic Agents"

A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (31 October 2015)

Special Issue Editors

Guest Editor
Dr. Ashkan Emadi

Leukemia and Hematologic Malignancies, Marlene & Stewart Greenebaum Cancer Center, School of Medicine, University of Maryland, Baltimore, Maryland 21201, USA
E-Mail
Interests: acute leukemia; myelodysplastic syndrome; myeloproliferative neoplasms; metabolic pathways and metabolism in hematologic malignancies; glutamine metabolism in cancer; anti-neoplastic effects of naphthoquinones; Chemotherapeutic Design and Discovery for Hematologic and Solid Neoplasms
Guest Editor
Dr. Dhimant Desai

Department of Pharmacology, Pennsylvania State University College of Medicine, 500 University Drive Hershey, PA 17033, USA
E-Mail
Phone: 7175316805
Interests: Synthesis of chemotherapeutic and chemopreventive agents; colon; melanoma; prostate; pancreatic; lung; drug discovery and delivery

Special Issue Information

Dear Colleagues,

The journal “Pharmaceuticals” is planning to publish a special issue covering the topic “Chemotherapeutic Agents” and we are inviting you to contribute an article to this volume. Cancer survival has improved drastically in the last four decades. This is the culmination of many factors, most importantly endless work of scientists and clinicians to better understand the pathophysiology of neoplastic cells. Cancer is an extremely heterogeneous disease with several distinct clinical, pathological, genetic, and molecular features. Although significant advances have been accomplished to treat a few cancers such as chronic myelogenous leukemia (CML), acute promyelocytic leukemia (APL), testicular cancer and lymphomas, much more basic, translational and clinical research are needed to fight other hematologic and solid neoplasms. The novel chemotherapeutic agents have revolutionaized our ability to fight cancer. The design and mechanisms of action of the chemotherapeutic agents, their biological activity screening in vitro and in vivo, and subsequent clinical trials are ongoing need of modern industrialized societies. We would like you to share your contributions to the advances and opportunities in this burgeoning field of cancer chemotherapy drug discovery and development for this special issue. Areas of interest include basic and clinical research on novel:

  • Alkylating agents
  • Anti-metabolites
  • Plant alkaloids including vincas, taxanes, podophyllotoxins
  • Topoisomerase inhibitors
  • Kinase signaling pathways and inhibitors
  • Intracellular Redox Modification
  • Targeting Cancer Metabolic Pathways Modulators
  • Monoclonal Antibodies
  • Nanotechnology Drug Delivery
  • Modulators of Tumor Microenvironments
  • Metal- and Metalloid-based Chemotherapy Agents
  • Epigenetic Modifications

Dr. Ashkan Emadi
Dr. Dhimant Desai
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 850 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.


Keywords

  • alkylating agents
  • anti-metabolites
  • plant alkaloids including vincas, taxanes, podophyllotoxins
  • topoisomerase inhibitors
  • kinase signaling pathways and inhibitors
  • intracellular redox modification
  • targeting cancer metabolic pathways modulators
  • monoclonal antibodies
  • nanotechnology drug delivery
  • modulators of tumor microenvironments
  • metal- and metalloid-based chemotherapy agents
  • epigenetic modifications

Published Papers (5 papers)

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Research

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Open AccessArticle A Selenium Containing Inhibitor for the Treatment of Hepatocellular Cancer
Pharmaceuticals 2016, 9(2), 18; https://doi.org/10.3390/ph9020018
Received: 4 January 2016 / Revised: 11 March 2016 / Accepted: 16 March 2016 / Published: 24 March 2016
Cited by 4 | PDF Full-text (2466 KB) | HTML Full-text | XML Full-text
Abstract
Hepatocellular carcinoma (HCC) is the third most deadly cancer in the world. New treatment strategies are desperately needed due to limited standard therapies. Activation of the Erk, Akt, and STAT3pathways is implicated in the prognosis of HCC. The Se,Se′-1,4-phenylenebis(1,2-ethanediyl) bisisoselenourea [...] Read more.
Hepatocellular carcinoma (HCC) is the third most deadly cancer in the world. New treatment strategies are desperately needed due to limited standard therapies. Activation of the Erk, Akt, and STAT3pathways is implicated in the prognosis of HCC. The Se,Se′-1,4-phenylenebis(1,2-ethanediyl) bisisoselenourea (PBISe), is a selenium-containing MAPK and PI3 kinase inhibitor, effectively inhibit tumorigenesis in a variety of experimental models. The aim of our study is to demonstrate the potential role of PBISe in the treatment of HCC. The anti-proliferative and pro-apoptotic ability of PBISe is studied in vitro in four human HCC cell lines and in vivo in a spontaneous murine HCC model. Inhibition of cancer growth was performed by cell viability assay and apoptosis by caspase 3/7, PARP cleavage, annexin-V, and TUNEL assays. Role of PBISe on PI3 kinase, MAPK and STAT3 signaling is determined by Western blotting. In vivo effects of PBISe on tumor sizes were monitored using MRI in a spontaneous murine HCC. Liver tissues from the PBISe-treated mice are analyzed for angiogenesis, proliferation, and signaling pathway markers. Overall, PBISe activated caspase-3/7 and increased DNA fragmentation, which is positively correlated with the increased PARP cleavage. PBISe promoted apoptosis by inhibiting PI3K, MAPK, and STAT3 signaling with significant reduction in the tumor sizes (p < 0.007). PBISe-treated tumors reduced survival marker PCNA, and angiogenesis markers Vegf-A, Vegf-R3 and CD34. These results demonstrate the chemotherapeutic effects of PBISe, by inhibiting tumor growth and facilitating tumor apoptosis for HCC treatment. Full article
(This article belongs to the Special Issue Chemotherapeutic Agents)
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Open AccessShort Note Minimally-Myelosuppressive Asparaginase-Containing Induction Regimen for Treatment of a Jehovah’s Witness with mutant IDH1/NPM1/NRAS Acute Myeloid Leukemia
Pharmaceuticals 2016, 9(1), 12; https://doi.org/10.3390/ph9010012
Received: 13 January 2016 / Revised: 19 February 2016 / Accepted: 8 March 2016 / Published: 10 March 2016
Cited by 4 | PDF Full-text (973 KB) | HTML Full-text | XML Full-text
Abstract
Treatment of patients with acute myeloid leukemia (AML) who do not wish to accept blood product transfusion, including Jehovah’s Witnesses, is extremely challenging. The use of conventional chemotherapy for induction of complete remission (CR) results in profound anemia and thrombocytopenia requiring frequent transfusions [...] Read more.
Treatment of patients with acute myeloid leukemia (AML) who do not wish to accept blood product transfusion, including Jehovah’s Witnesses, is extremely challenging. The use of conventional chemotherapy for induction of complete remission (CR) results in profound anemia and thrombocytopenia requiring frequent transfusions of blood products, without which such treatment will be life-threatening. Finding a well tolerable, minimally myelosuppressive induction regimen for such patients with AML is a clear example of area of unmet medical need. Here, we report a successful treatment of a 52-year-old Jehovah’s Witness with newly diagnosed AML with peg-asparaginase, vincristine and methylprednisolone. The AML was characterized with normal karyotype, and mutations in isocitrate dehydrogenase 1 (IDH1-Arg132Ser), nucleophosmin 1 (NPM1-Trp289Cysfs*12) and neuroblastoma RAS viral oncogene homolog (NRAS-G1y12Va1). After one 28-day cycle of treatment, the patient achieved complete remission with incomplete count recovery (CRi) and after the second cycle, he achieved CR with full blood count recovery. The patient has never received any blood products. Notwithstanding that myeloperoxidase-induced oxidative degradation of vincristine results in its lack of activity as monotherapy in AML, its combination with corticosteroid and asparaginase has resulted in a robust remission in this patient. Diminished steroid clearance by asparaginase activity as well as reduction in serum glutamine level induced by glutaminase enzymatic activity of asparaginase may have contributed to effective killing of the myeloblasts that carry IDH1/NPM1/NRAS mutations. In conclusion, asparaginase-containing regimens, which are approved for treatment of acute lymphoblastic leukemia (ALL) but not AML, can be used to treat patients with AML who do not accept blood transfusion. Full article
(This article belongs to the Special Issue Chemotherapeutic Agents)
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Open AccessArticle Hydroxylated Dimeric Naphthoquinones Increase the Generation of Reactive Oxygen Species, Induce Apoptosis of Acute Myeloid Leukemia Cells and Are Not Substrates of the Multidrug Resistance Proteins ABCB1 and ABCG2
Pharmaceuticals 2016, 9(1), 4; https://doi.org/10.3390/ph9010004
Received: 30 November 2015 / Revised: 7 January 2016 / Accepted: 14 January 2016 / Published: 19 January 2016
Cited by 3 | PDF Full-text (2602 KB) | HTML Full-text | XML Full-text
Abstract
Selective targeting of the oxidative state, which is a tightly balanced fundamental cellular property, is an attractive strategy for developing novel anti-leukemic chemotherapeutics with potential applications in the treatment of acute myeloid leukemia (AML), a molecularly heterogeneous disease. Dimeric naphthoquinones (BiQs) with the [...] Read more.
Selective targeting of the oxidative state, which is a tightly balanced fundamental cellular property, is an attractive strategy for developing novel anti-leukemic chemotherapeutics with potential applications in the treatment of acute myeloid leukemia (AML), a molecularly heterogeneous disease. Dimeric naphthoquinones (BiQs) with the ability to undergo redox cycling and to generate reactive oxygen species (ROS) in cancer cells are a novel class of compounds with unique characteristics that make them excellent candidates to be tested against AML cells. We evaluated the effect of two BiQ analogues and one monomeric naphthoquinone in AML cell lines and primary cells from patients. All compounds possess one halogen and one hydroxyl group on the quinone cores. Dimeric, but not monomeric, naphthoquinones demonstrated significant anti-AML activity in the cell lines and primary cells from patients with favorable therapeutic index compared to normal hematopoietic cells. BiQ-1 effectively inhibited clonogenicity and induced apoptosis as measured by Western blotting and Annexin V staining and mitochondrial membrane depolarization by flow cytometry. BiQ-1 significantly enhances intracellular ROS levels in AML cells and upregulates expression of key anti-oxidant protein, Nrf2. Notably, systemic exposure to BiQ-1 was well tolerated in mice. In conclusion, we propose that BiQ-induced therapeutic augmentation of ROS in AML cells with dysregulation of antioxidants kill leukemic cells while normal cells remain relatively intact. Further studies are warranted to better understand this class of potential chemotherapeutics. Full article
(This article belongs to the Special Issue Chemotherapeutic Agents)
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Review

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Open AccessReview Targeting Cell Survival Proteins for Cancer Cell Death
Pharmaceuticals 2016, 9(1), 11; https://doi.org/10.3390/ph9010011
Received: 3 December 2015 / Revised: 8 February 2016 / Accepted: 16 February 2016 / Published: 25 February 2016
Cited by 12 | PDF Full-text (1730 KB) | HTML Full-text | XML Full-text
Abstract
Escaping from cell death is one of the adaptations that enable cancer cells to stave off anticancer therapies. The key players in avoiding apoptosis are collectively known as survival proteins. Survival proteins comprise the Bcl-2, inhibitor of apoptosis (IAP), and heat shock protein [...] Read more.
Escaping from cell death is one of the adaptations that enable cancer cells to stave off anticancer therapies. The key players in avoiding apoptosis are collectively known as survival proteins. Survival proteins comprise the Bcl-2, inhibitor of apoptosis (IAP), and heat shock protein (HSP) families. The aberrant expression of these proteins is associated with a range of biological activities that promote cancer cell survival, proliferation, and resistance to therapy. Several therapeutic strategies that target survival proteins are based on mimicking BH3 domains or the IAP-binding motif or competing with ATP for the Hsp90 ATP-binding pocket. Alternative strategies, including use of nutraceuticals, transcriptional repression, and antisense oligonucleotides, provide options to target survival proteins. This review focuses on the role of survival proteins in chemoresistance and current therapeutic strategies in preclinical or clinical trials that target survival protein signaling pathways. Recent approaches to target survival proteins-including nutraceuticals, small-molecule inhibitors, peptides, and Bcl-2-specific mimetic are explored. Therapeutic inventions targeting survival proteins are promising strategies to inhibit cancer cell survival and chemoresistance. However, complete eradication of resistance is a distant dream. For a successful clinical outcome, pretreatment with novel survival protein inhibitors alone or in combination with conventional therapies holds great promise. Full article
(This article belongs to the Special Issue Chemotherapeutic Agents)
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Open AccessReview The Role of Immunotherapy in Multiple Myeloma
Pharmaceuticals 2016, 9(1), 3; https://doi.org/10.3390/ph9010003
Received: 11 November 2015 / Revised: 29 December 2015 / Accepted: 6 January 2016 / Published: 14 January 2016
Cited by 12 | PDF Full-text (389 KB) | HTML Full-text | XML Full-text
Abstract
Multiple myeloma is the second most common hematologic malignancy. The treatment of this disease has changed considerably over the last two decades with the introduction to the clinical practice of novel agents such as proteasome inhibitors and immunomodulatory drugs. Basic research efforts towards [...] Read more.
Multiple myeloma is the second most common hematologic malignancy. The treatment of this disease has changed considerably over the last two decades with the introduction to the clinical practice of novel agents such as proteasome inhibitors and immunomodulatory drugs. Basic research efforts towards better understanding of normal and missing immune surveillence in myeloma have led to development of new strategies and therapies that require the engagement of the immune system. Many of these treatments are under clinical development and have already started providing encouraging results. We, for the second time in the last two decades, are about to witness another shift of the paradigm in the management of this ailment. This review will summarize the major approaches in myeloma immunotherapies. Full article
(This article belongs to the Special Issue Chemotherapeutic Agents)
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