Combination Therapy with Arsenic Trioxide for Hematological Malignancies

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)


Volume 16, 12 Issues, 2016


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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
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Combination Therapy with Arsenic Trioxide for Hematological Malignancies



Anti-Cancer Agents in Medicinal Chemistry, 10(6): 504-510.

Author(s): Shinichiro Takahashi.

Affiliation: Division of Hematology, Kitasato University School of Allied Health Sciences, 1-15-1 Kitasato, Minami-ku, Sagamihara 252-0373, Japan.

Abstract

Arsenic trioxide (ATO) has shown great promise in the treatment of patients with relapsed or refractory acute promyelocytic leukemia (APL). However, the risk/benefit ratios of ATO in hematologic malignancies other than APL are still unclear. In this review, the author attempts to provide current experimental and clinical challenges to gain more knowledge of the effects of ATO by examining combination therapies with other agents, especially for non-APL hematologic malignancies, such as acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), chronic myeloid leukemia (CML), chronic lymphoid leukemia (CLL) and multiple myeloma (MM). The drugs combined with ATO can be roughly classified into (1) signaling inhibitors (imatinib, PD184352, LY294002, 17-Allylamino- 17-demethoxygeldanamycin: 17-AAG), (2) oxidative stress pathway modulators (ascorbic acid, 2-methoxyestradiol: 2-ME, dlbuthionine-[ S,R]-sulfoximine: BSO), (3) a chemotherapeutic drug (melphalan) and (4) others (bortezomib, ATRA). Some of these combination therapies have shown promising results in MM not only at the experimental level but also at the clinical level. However, studies are still ongoing for other non-APL hematologic malignancies. Since ATO is well tolerated and its toxicities are manageable and reversible, cell type-specific and efficient combination therapies with ATO are advantageous for non-APL hematological malignancies and should be developed in the near future.

Keywords:

Acute lymphoid leukemia, acute myeloid leukemia, arsenic trioxide, chronic lymphoid leukemia, chronic myeloid leukemia, combination therapy, multiple myeloma, Hematological Malignancies, acute promyelocytic leukemia, imatinib, PD184352, LY294002, 17-Allylamino-17-demethoxygeldanamycin, oxidative stress pathway modulators, ascorbic acid, 2-methoxyestradiol, dlbuthionine-[S,R]-sulfoximine, potassium bicarbonate, Thomas Fowler's solution, all-trans retinoic acid, promyelocytic leukemia, retinoic acid receptor a, myeloma cells, MYELODYSPLASTIC SYNDROME, hematologic malignancies, extracellular signal-regulated kinase, Fms-like tyrosine kinase 3, glucocorticoid-resistant ALL cells, antineoplastic agents, Bcr-Abl-positive leukemic cells, cytochrome c, NF-κB, IκB kinase, small ubiquitin-like protein modifier (SUMO)-conjugating enzyme 9, SUMOylation.



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Article Details

Volume: 10
Issue Number: 6
First Page: 504
Last Page: 510
Page Count: 7
DOI: 10.2174/1871520611009060504
Price: $58
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