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- Friedman, Ran
(författare)
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The molecular mechanisms behind activation of FLT3 in acute myeloid leukemia and resistance to therapy by selective inhibitors
- 2022
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Ingår i: Biochimica et Biophysica Acta. CR. Reviews on Cancer. - : Elsevier. - 0304-419X .- 1879-2561. ; 1877:1
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Tidskriftsartikel (refereegranskat)abstract
- Acute myeloid leukemia is an aggressive cancer, which, in spite of increasingly better understanding of its genetic background remains difficult to treat. Mutations in the FLT3 gene are observed in ≈30% of the patients. Most of these mutations are internal tandem duplications (ITDs) of a sequence within the protein coding region, an activation mechanism that is almost non-existent with other genes and cancers. As patients each carry their own unique set of mutations, it is challenging to understand how ITDs activate the protein, and ascertain the risk for each individual patient. Available treatment options are limited due to development of drug resistance. Here, recent studies are reviewed that help to better understand the molecular mechanism behind activation of the FLT3 protein due to mutations. It is argued that difference in mutation sequences and especially location might be coupled to prognosis. When it comes to FLT3 inhibitors, key differences between them can be attributed to the mode of inhibition (type-1 and type-2 inhibitors), effective inhibitory coefficient in the blood plasma and off-target binding. Accounting for the position and length of insertions may in the future be used to predict prognosis and rationalise treatment. Development of new inhibitors must take into account the potential for resistance mutations. Inhibitors aimed at multiple specific targets are currently being developed. These, and as well as combination therapies will hopefully lead to longer periods during which targeted FLT3 therapy will remain effective.
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| 2. |
- Mishra, Abhay, et al.
(författare)
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A tale of exosomes and their implication in cancer
- 2023
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Ingår i: Biochimica et Biophysica Acta - Reviews on Cancer. - : Elsevier. - 0304-419X .- 1879-2561. ; 1878:4
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Forskningsöversikt (refereegranskat)abstract
- Cancer is a cause of high deaths worldwide and also a huge burden for the health system. Cancer cells have unique properties such as a high rate of proliferation, self-renewal, metastasis, and treatment resistance, therefore, the development of novel diagnoses of cancers is a tedious task. Exosomes are secreted by virtually all cell types and have the ability to carry a multitude of biomolecules crucial for intercellular communication, hence, contributing a crucial part in the onset and spread of cancer. These exosomal components can be utilized in the development of markers for diagnostic and prognostic purposes for various cancers. This review emphasized primarily the following topics: exosomes structure and functions, isolation and characterization strategies of exosomes, the role of exosomal contents in cancer with a focus in particular on noncoding RNA and protein, exosomes, and the cancer microenvironment interactions, cancer stem cells, and tumor diagnosis and prognosis based on exosomes.
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