Actionable Vulnerabilities in Hematological Malignancies

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Pathophysiology".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 6333

Special Issue Editors

Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy
Interests: cancer; epigenetics; miRNA; non-coding RNA; hematological malignancies
Special Issues, Collections and Topics in MDPI journals
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
Interests: long noncoding RNA (lncRNA); microRNA (miRNA); multiple myeloma; plasma cell dyscrasias; RNA therapeutics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The integration of multi-omics approaches with extensive genetic and pharmacologic screens has provided a comprehensive view of the vulnerabilities (or “dependencies”) featuring human cancers. The concurrent advancement in chemical biology and drug development has been projecting the scientific community towards an unprecedented scenario whereby any disease-associated factor may become druggable.

This special issue will focus on present understanding of the actionability of hematological cancer dependencies, including both cancer cell-intrinsic and tumor microenvironment-mediated mechanisms. We invite authors to contribute original research articles, communications as well as review articles. Potential topics include (but are not limited to) the discovery, characterization, and targeting of:

  • Genetic, epigenetic, and transcriptional dependencies
  • Metabolic dependencies
  • Tumor microenvironment-mediated dependencies
  • Co-dependency networks and circuitries
  • Dependency to non-protein coding genes
  • Synthetic lethal dependencies

Dr. Nicola Amodio
Dr. Eugenio Morelli
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • hematology
  • cancer
  • leukemia
  • lymphoma
  • plasma cell dyscrasias
  • multiple myeloma
  • oncogene addiction
  • cancer dependency
  • genetics
  • epigenetics
  • transcriptomics
  • tumor metabolism
  • tumor microenvironment
  • noncoding RNA
  • RNA therapeutics

Published Papers (3 papers)

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Research

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17 pages, 2944 KiB  
Article
TRIM10 Is Downregulated in Acute Myeloid Leukemia and Plays a Tumor Suppressive Role via Regulating NF-κB Pathway
by Lin Li, Qi Li, Zhengrong Zou, Zoufang Huang and Yijian Chen
Cancers 2023, 15(2), 417; https://doi.org/10.3390/cancers15020417 - 08 Jan 2023
Cited by 1 | Viewed by 1639
Abstract
Background: Accumulating evidence suggests that members of the tripartite motif (TRIMs) family play a crucial role in the development and progression of hematological malignancy. Here, we explored the expression and potential role of TRIM10 in acute myeloid leukemia (AML). Methods: The expression levels [...] Read more.
Background: Accumulating evidence suggests that members of the tripartite motif (TRIMs) family play a crucial role in the development and progression of hematological malignancy. Here, we explored the expression and potential role of TRIM10 in acute myeloid leukemia (AML). Methods: The expression levels of TRIM10 were investigated in AML patients and cell lines by RNA-seq, qRT-PCR and Western blotting analysis. Lentiviral infection was used to regulate the level of TRIM10 in AML cells. The effects of TRIM10 on apoptosis, drug sensitivity and proliferation of AML cells were evaluated by flow cytometry and cell-counting kit-8 (CCK-8) assay, as well as being assessed in a murine model. Results: TRIM10 mRNA and protein expression was reduced in primary AML samples and AML cell lines in comparison to the normal controls and a human normal hematopoietic cell line, respectively. Moreover, overexpression of TRIM10 in HL60 and K562 cells inhibited AML cell proliferation and induced cell apoptosis. The nude mice study further confirmed that overexpression of TRIM10 blocked tumor growth and inhibited cell proliferation. In contrast, knockdown of TRIM10 in AML cells showed contrary results. Subsequent mechanistic studies demonstrated that knockdown of TRIM10 enhanced the expression of nuclear protein P65, which implied the activation of the NF-κB signal pathway. Consistently, overexpression of TRIM10 in AML cells showed a contrary result. These data indicated that inactivation of the NF-κB pathway is involved in TRIM10-mediated regulation in AML. TRIM10 expression can be de-repressed by a combination that targets both DNA methyltransferase and histone deacetylase. Conclusions: Our results strongly suggested that TRIM10 plays a tumor suppressive role in AML development associated with the NF-κB signal pathway and may be a potential target of epigenetic therapy against leukemia. Full article
(This article belongs to the Special Issue Actionable Vulnerabilities in Hematological Malignancies)
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Review

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13 pages, 610 KiB  
Review
Optimizing Treatment Options for Newly Diagnosed Acute Myeloid Leukemia in Older Patients with Comorbidities
by Gaku Oshikawa and Koji Sasaki
Cancers 2023, 15(8), 2399; https://doi.org/10.3390/cancers15082399 - 21 Apr 2023
Cited by 1 | Viewed by 1625
Abstract
Traditionally, the goal of AML therapy has been to induce remission through intensive chemotherapy, maintain long-term remission using consolidation therapy, and achieve higher rates of a cure by allogeneic transplantation in patients with a poor prognosis. However, for the elderly patients and those [...] Read more.
Traditionally, the goal of AML therapy has been to induce remission through intensive chemotherapy, maintain long-term remission using consolidation therapy, and achieve higher rates of a cure by allogeneic transplantation in patients with a poor prognosis. However, for the elderly patients and those with comorbidities, the toxicity often surpasses the therapeutic benefits of intensive chemotherapy. Consequently, low-intensity therapies, such as the combination of a hypomethylating agent with venetoclax, have emerged as promising treatment options for elderly patients. Given the rise of low-intensity therapies as the leading treatment option for the elderly, it is increasingly important to consider patients’ age and comorbidities when selecting a treatment option. The recently proposed comorbidity-based risk stratification for AML allows prognosis stratification not only in patients undergoing intensive chemotherapy, but also in those receiving low-intensity chemotherapy. Optimizing treatment intensity based on such risk stratification is anticipated to balance treatment efficacy and safety, and will ultimately improve the life expectancy for patients with AML. Full article
(This article belongs to the Special Issue Actionable Vulnerabilities in Hematological Malignancies)
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15 pages, 1030 KiB  
Review
Targeting BCMA in Multiple Myeloma: Advances in Antibody-Drug Conjugate Therapy
by Lijie Xing, Yuntong Liu and Jiye Liu
Cancers 2023, 15(8), 2240; https://doi.org/10.3390/cancers15082240 - 11 Apr 2023
Cited by 2 | Viewed by 2204
Abstract
Multiple myeloma (MM) is an incurable cancer of the plasma cells. In the last twenty years, treatment strategies have evolved toward targeting MM cells—from the shotgun chemotherapy approach to the slightly more targeted approach of disrupting important MM molecular pathways to the immunotherapy [...] Read more.
Multiple myeloma (MM) is an incurable cancer of the plasma cells. In the last twenty years, treatment strategies have evolved toward targeting MM cells—from the shotgun chemotherapy approach to the slightly more targeted approach of disrupting important MM molecular pathways to the immunotherapy approach that specifically targets MM cells based on protein expression. Antibody-drug conjugates (ADCs) are introduced as immunotherapeutic drugs which utilize an antibody to deliver cytotoxic agents to cancer cells distinctively. Recent investigations of ADCs for MM treatment focus on targeting B cell maturation antigen (BCMA), which regulates B cell proliferation, survival, maturation, and differentiation into plasma cells (PCs). Given its selective expression in malignant PCs, BCMA is one of the most promising targets in MM immunotherapy. Compared to other BCMA-targeting immunotherapies, ADCs have several benefits, such as lower price, shorter production period, fewer infusions, less dependence on the patient’s immune system, and they are less likely to over-activate the immune system. In clinical trials, anti-BCMA ADCs have shown safety and remarkable response rates in patients with relapsed and refractory MM. Here, we review the properties and clinical applications of anti-BCMA ADC therapies and discuss the potential mechanisms of resistance and ways to overcome them. Full article
(This article belongs to the Special Issue Actionable Vulnerabilities in Hematological Malignancies)
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