Myeloid malignancies, including myeloid leukemia, myeloproliferative neoplasm (MPN) and myelodysplastic syndrome (MDS), is a heterogeneous disorder characterized by clonal expansion of myeloid progenitors (blasts) and represent about 5% of all adult cancers. Myeloid leukemia is among one of the best studied human cancers. Philadelphia chromosome in chronic myeloid leukemia is the first consistent chromosome abnormality found in any kind of malignancy. Acute myeloid leukemia (AML) is one of the first cancers to be sequenced at the level of the whole genome. Recent years have witnessed the accumulation of unprecedented amounts of genomic data, revealing the tremendous biological complexity of the disease, dictated in part by mutational, clonal, and epigenetic heterogeneity. Despite recent advances in the biology and genetic landscape of myeloid malignancies, the clinical outcome of patients remains poor. The challenge of translating the scientific discoveries into effective therapies for patients with myeloid malignancies constituted an urgent unmet medical need.
It has been almost a hundred years since Otto Warburg reported the Warburg effect, which describe preference of cancer cells to use anaerobic glycolysis rather than the oxidative phosphorylation. Since then, substantial investigational efforts have been invested both by the scientists and clinicians on the discrepancies of metabolism between cancer cells and their normal counterparts in utilizing nutrients to spur tumor growth. In 1947, in children with acute lymphoblastic leukemia, Sidney Farber pioneered the use of aminopterin, precursor of the currently used drugs methotrexate, which is a folate analog that inhibit one-carbon transfer required for de novo nucleotide synthesis. It is clear that understanding cancer metabolism can improve cancer therapy, as exemplified by the widespread use of 18-fluorodeoxyglucose, a glucose analog that exploits the Warburg effect in PET imaging for cancer diagnosis, treatment, and prognosis. Increased dependence on certain metabolic pathway exposes the vulnerability of cancer cells. From a therapeutic perspective, the aberrant metabolism of proliferating cancer cells presents therapeutic window, and there has been a growing body of interest in studying how best to target altered glucose metabolism, upregulated glutaminolysis, increased dependence on serine, dysfunctional de novo lipid synthesis and rising requirement for detoxification of reactive metabolites. During the last 20 years there has be few FDA- approved drugs for AML, until in 2017, when enasidenib was sanctioned as a first-in-class inhibitor of IDH2, offering encouragement that more breakthroughs are coming. This special issue focuses on our current understanding of cancer metabolism and discuss how this might guide treatments targeting the metabolic vulnerability in myeloid malignancies, in particular metabolic alterations associated with resistance toward different anticancer agents.
We welcome submissions of Original Research, Clinical Trial articles, and Reviews on myeloid malignancies focusing on but not limited to the following subtopics:
? Targeting amino acid metabolism in myeloid malignancies.
? Targeting nucleotide metabolism in myeloid malignancies.
? Targeting Redox metabolism in myeloid malignancies.
? Targeting iron metabolism in myeloid malignancies.
? Targeting autophagy in Cancer Metabolism
? Targeting Cancer-Immune interplay.
? Targeting Cancer- microenvironment interaction.
? Metabolic determinants of myeloid transformation.
Myeloid malignancies, including myeloid leukemia, myeloproliferative neoplasm (MPN) and myelodysplastic syndrome (MDS), is a heterogeneous disorder characterized by clonal expansion of myeloid progenitors (blasts) and represent about 5% of all adult cancers. Myeloid leukemia is among one of the best studied human cancers. Philadelphia chromosome in chronic myeloid leukemia is the first consistent chromosome abnormality found in any kind of malignancy. Acute myeloid leukemia (AML) is one of the first cancers to be sequenced at the level of the whole genome. Recent years have witnessed the accumulation of unprecedented amounts of genomic data, revealing the tremendous biological complexity of the disease, dictated in part by mutational, clonal, and epigenetic heterogeneity. Despite recent advances in the biology and genetic landscape of myeloid malignancies, the clinical outcome of patients remains poor. The challenge of translating the scientific discoveries into effective therapies for patients with myeloid malignancies constituted an urgent unmet medical need.
It has been almost a hundred years since Otto Warburg reported the Warburg effect, which describe preference of cancer cells to use anaerobic glycolysis rather than the oxidative phosphorylation. Since then, substantial investigational efforts have been invested both by the scientists and clinicians on the discrepancies of metabolism between cancer cells and their normal counterparts in utilizing nutrients to spur tumor growth. In 1947, in children with acute lymphoblastic leukemia, Sidney Farber pioneered the use of aminopterin, precursor of the currently used drugs methotrexate, which is a folate analog that inhibit one-carbon transfer required for de novo nucleotide synthesis. It is clear that understanding cancer metabolism can improve cancer therapy, as exemplified by the widespread use of 18-fluorodeoxyglucose, a glucose analog that exploits the Warburg effect in PET imaging for cancer diagnosis, treatment, and prognosis. Increased dependence on certain metabolic pathway exposes the vulnerability of cancer cells. From a therapeutic perspective, the aberrant metabolism of proliferating cancer cells presents therapeutic window, and there has been a growing body of interest in studying how best to target altered glucose metabolism, upregulated glutaminolysis, increased dependence on serine, dysfunctional de novo lipid synthesis and rising requirement for detoxification of reactive metabolites. During the last 20 years there has be few FDA- approved drugs for AML, until in 2017, when enasidenib was sanctioned as a first-in-class inhibitor of IDH2, offering encouragement that more breakthroughs are coming. This special issue focuses on our current understanding of cancer metabolism and discuss how this might guide treatments targeting the metabolic vulnerability in myeloid malignancies, in particular metabolic alterations associated with resistance toward different anticancer agents.
We welcome submissions of Original Research, Clinical Trial articles, and Reviews on myeloid malignancies focusing on but not limited to the following subtopics:
? Targeting amino acid metabolism in myeloid malignancies.
? Targeting nucleotide metabolism in myeloid malignancies.
? Targeting Redox metabolism in myeloid malignancies.
? Targeting iron metabolism in myeloid malignancies.
? Targeting autophagy in Cancer Metabolism
? Targeting Cancer-Immune interplay.
? Targeting Cancer- microenvironment interaction.
? Metabolic determinants of myeloid transformation.
