Repurposing Drugs for Acute Myeloid Leukemia: A Worthy Cause or a Futile Pursuit?

Wojcicki, Anna V.; Kadapakkam, Meena; Frymoyer, Adam; Lacayo, Norman J.; Chae, Hee-Don; Sakamoto, Kathleen M.

doi:10.3390/cancers12020441

Cited by 17 publications

(14 citation statements)

References 101 publications

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“…Another set of structural variants of interest for anti-cancer drug repurposing is that of gene fusions. Perhaps the paradigmatic case is that of acute myeloid leukemia (AML) ( 168 ). The case of niclosamide is relevant since it targets some relatively common gene fusions (or their associated chimeric proteins), aside from targeting relevant transcription factors such as CREB, STAT3 and NF- κ B. Chromosomal aberrations and gene fusions in intimal sarcoma have also helped to identify potential therapeutic targets ( 169 ).…”

Section: Discussionmentioning

confidence: 99%

Pathway-Based Drug-Repurposing Schemes in Cancer: The Role of Translational Bioinformatics

Hernández‐Lemus

Martínez-García

2021

Front. Oncol.

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Cancer is a set of complex pathologies that has been recognized as a major public health problem worldwide for decades. A myriad of therapeutic strategies is indeed available. However, the wide variability in tumor physiology, response to therapy, added to multi-drug resistance poses enormous challenges in clinical oncology. The last years have witnessed a fast-paced development of novel experimental and translational approaches to therapeutics, that supplemented with computational and theoretical advances are opening promising avenues to cope with cancer defiances. At the core of these advances, there is a strong conceptual shift from gene-centric emphasis on driver mutations in specific oncogenes and tumor suppressors—let us call that the silver bullet approach to cancer therapeutics—to a systemic, semi-mechanistic approach based on pathway perturbations and global molecular and physiological regulatory patterns—we will call this the shrapnel approach. The silver bullet approach is still the best one to follow when clonal mutations in driver genes are present in the patient, and when there are targeted therapies to tackle those. Unfortunately, due to the heterogeneous nature of tumors this is not the common case. The wide molecular variability in the mutational level often is reduced to a much smaller set of pathway-based dysfunctions as evidenced by the well-known hallmarks of cancer. In such cases “shrapnel gunshots” may become more effective than “silver bullets”. Here, we will briefly present both approaches and will abound on the discussion on the state of the art of pathway-based therapeutic designs from a translational bioinformatics and computational oncology perspective. Further development of these approaches depends on building collaborative, multidisciplinary teams to resort to the expertise of clinical oncologists, oncological surgeons, and molecular oncologists, but also of cancer cell biologists and pharmacologists, as well as bioinformaticians, computational biologists and data scientists. These teams will be capable of engaging on a cycle of analyzing high-throughput experiments, mining databases, researching on clinical data, validating the findings, and improving clinical outcomes for the benefits of the oncological patients.

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Section: Discussionmentioning

confidence: 99%

Pathway-Based Drug-Repurposing Schemes in Cancer: The Role of Translational Bioinformatics

Hernández‐Lemus

Martínez-García

2021

Front. Oncol.

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“…Hardly. A very recent review on drug repurposing in AML asked if it were a futile pursuit and responded by saying that even a failed attempt furthers our knowledge of AML biology [ 174 ].…”

Section: Does the Promise Hold?mentioning

confidence: 99%

Has Drug Repurposing Fulfilled Its Promise in Acute Myeloid Leukaemia?

Valli¹,

Gruszka-Westwood²,

Alcalay³

2020

JCM

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Drug repurposing is a method of drug discovery that consists of finding a new therapeutic context for an old drug. Compound identification arises from screening of large libraries of active compounds, through interrogating databases of cell line gene expression response upon treatment or by merging several types of information concerning disease–drug relationships. Although, there is a general consensus on the potential and advantages of this drug discovery modality, at the practical level to-date no non-anti-cancer repurposed compounds have been introduced into standard acute myeloid leukaemia (AML) management, albeit that preclinical validation yielded several candidates. The review presents the state-of-the-art drug repurposing approach in AML and poses the question of what has to be done in order to take a full advantage of it, both at the stage of screening design and later when progressing from the preclinical to the clinical phases of drug development. We argue that improvements are needed to model and read-out systems as well as to screening technologies, but also to more funding and trust in drug repurposing strategies.

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“…Metastatic brain cancer (tumor) treatment requires crucial medication parameters of non-chemotherapeutics, chemotherapeutics, radiation and surgical techniques [11]. Non-chemotherapeutic drugs are preferred to relieve tumor-associated headache and epileptic seizures [12,13]. However, chemotherapeutic drugs help in mitigating tumor mass and edema as well as killing cancer cells [14].…”

Section: Introductionmentioning

confidence: 99%

Nanomaterials for Diagnosis and Treatment of Brain Cancer: Recent Updates

et al. 2020

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Brain tumors, especially glioblastoma, remain the most aggressive form of all the cancers because of inefficient diagnosis and profiling. Nanostructures, such as metallic nanostructures, silica nano-vehicles, quantum dots, lipid nanoparticles (NPs) and polymeric NPs, with high specificity have made it possible to permeate the blood–brain barrier (BBB). NPs possess optical, magnetic and photodynamic properties that can be exploited by surface modification, bio composition, contrast agents’ encapsulation and coating by tumor-derived cells. Hence, nanotechnology has brought on a revolution in the field of diagnosis and imaging of brain tumors and cancers. Recently, nanomaterials with biomimetic functions have been introduced to efficiently cross the BBB to be engulfed by deep skin tumors and cancer malignancies for imaging. The review focuses on nanotechnology-based diagnostic and imaging approaches for exploration in brain tumors and cancers. Moreover, the review also summarizes a few strategies to image glioblastoma and cancers by multimodal functional nanocomposites for more precise and accurate clinical diagnosis. Their unique physicochemical attributes, including nanoscale sizes, larger surface area, explicit structural features and ability to encapsulate diverse molecules on their surface, render nanostructured materials as excellent nano-vehicles to cross the blood–brain barrier and convey drug molecules to their target region. This review sheds light on the current progress of various kinds of nanomaterials, such as liposomes, nano-micelles, dendrimers, carbon nanotubes, carbon dots and NPs (gold, silver and zinc oxide NPs), for efficient drug delivery in the treatment and diagnosis of brain cancer.

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Repurposing Drugs for Acute Myeloid Leukemia: A Worthy Cause or a Futile Pursuit?

Cited by 17 publications

References 101 publications

Pathway-Based Drug-Repurposing Schemes in Cancer: The Role of Translational Bioinformatics

Pathway-Based Drug-Repurposing Schemes in Cancer: The Role of Translational Bioinformatics

Has Drug Repurposing Fulfilled Its Promise in Acute Myeloid Leukaemia?

Nanomaterials for Diagnosis and Treatment of Brain Cancer: Recent Updates

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