LSD1 as a Biomarker and the Outcome of Its Inhibitors in the Clinical Trial: The Therapy Opportunity in Tumor

Abstract

Tumors are the foremost cause of death worldwide. As a result of that, there has been a significant enhancement in the investigation, treatment methods, and good maintenance practices on cancer. However, the sensitivity and specificity of a lot of tumor biomarkers are not adequate. Hence, it is of inordinate significance to ascertain novel biomarkers to forecast the prognosis and therapy targets for tumors. This review characterized LSD1 as a biomarker in different tumors. LSD1 inhibitors in clinical trials were also discussed. The recent pattern advocates that LSD1 is engaged at sauce chromatin zones linking with complexes of multi-protein having an exact DNA-binding transcription factor, establishing LSD1 as a favorable epigenetic target, and also gives a large selection of therapeutic targets to treat different tumors. This review sturdily backing the oncogenic probable of LSD1 in different tumors indicated that LSD1 levels can be used to monitor and identify different tumors and can be a useful biomarker of progression and fair diagnosis in tumor patients. The clinical trials showed that inhibitors of LSD1 have growing evidence of clinical efficacy which is very encouraging and promising. However, for some of the inhibitors such as GSK2879552, though selective, potent, and effective, its disease control was poor as the rate of adverse events (AEs) was high in tumor patients causing clinical trial termination, and continuation could not be supported by the risk-benefit profile. Therefore, we propose that, to attain excellent clinical results of inhibitors of LSD1, much attention is required in designing appropriate dosing regimens, developing in-depth in vitro/in vivo mechanistic works of LSD1 inhibitors, and developing inhibitors of LSD1 that are reversible, safe, potent, and selective which may offer safer profiles.

Systematic Review and Meta-Analysis of Lysine-Specific Demethylase 1 Expression as a Prognostic Biomarker of Cancer Survival and Disease Progression

“…Some of these drugs have entered clinical studies for tumor malignancies, including ORY-1001, CC-90011, INCB059872, TCP, GSK-2879552, IMG-7289, and ORY-2001. 5 Thrombocytopenia has been considered the most prevalent treatment-related adverse event with LSD1 inhibitors in clinical studies. The study by Johnston et al 81 attributed this toxicity to megakaryocytic stem cells.…”

“…Lysine-specific demethylase 1 is a monoamine oxidase homolog, which precisely removes methyl groups of H3K4/H3K9, thus triggering activation or suppression of genes. 3 - 5 Lysine-specific demethylase 1 control of gene expression has been revealed to be vital to manifold procedures together with organogenesis and stem cell differentiation. 6 , 7 Lysine-specific demethylase 1 plays a key role in non-histone proteins by getting rid of mono- and di-methylation which could be linked to tumor progression.…”

“…10,21,22 Hence, LSD1 has become an important therapeutic target for cancer therapy. 5,23 Some researchers assessing the prognostic significance of LSD1 in numerous tumor cells asserted that over-expression of LSD1 can be linked to poorer results among tumor patients. 21,24 However, results from other works are inconsistent.…”

The Role of Lysine-Specific Demethylase 1 (LSD1) in Shaping the Endothelial Inflammatory Response

“…Analysis of LSD1 biochemistry in physiological and pathological states have revealed that it is an orchestra protein, significantly involved in the regulation of cellular metabolism, based on its methyl group eraser activity and broad substrate specificity, which includes histone proteins (H3K4/9me) but also DNMT1, p53, STAT3, and E2F1, all of which play an important role in controlling the gene expression machinery [31]. The demethylase plays a particular role in cancer medicine as overexpression of LSD1 has been found in many types of cancer [18,32,33]. In consequence of detailed studies and identified effects on e.g.…”

Combining LSD1 and JAK-STAT inhibition targets Down syndrome-associated myeloid leukemia at its core

“…13,[17][18][19][20][21][22][23] Consequently, various irreversible LSD1 inhibitors have been developed in recent years, with some currently undergoing clinical trials for AML. [24][25][26][27] To further enhance the anti-leukemic effects of existing treatments, various drug combinations containing LSD1 inhibitors have been studied to date, and shown synergy in the induction of differentiation and cytotoxicity, e.g. in combination with azacitidine, retinoic acid, mTOR or BET inhibitors.…”