PIM Kinases in Multiple Myeloma

Wu, Jian; Chu, Emily Y.; Kang, Yubin

doi:10.3390/cancers13174304

Cited by 18 publications

(15 citation statements)

References 88 publications

(85 reference statements)

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“…Transgenic mouse models and overexpression studies in cell lines have confirmed that pim kinase is involved in the transduction of many cellular signaling pathways, thereby promoting tumorigenesis, especially in blood tissues. This supports the hypothesis that pim kinase inhibitors are small molecular inhibitors for MM patient therapy 2,69 . Newly discovered pan‐pim kinase inhibitors, such as pim447, are presently entering clinical trials that have demonstrated positive effects in MM.…”

Section: Clinical Efficacy Of Pim Kinase Inhibitors In MMsupporting

confidence: 67%

“…The family of pim kinases comprises three isozymes: pim‐1, pim‐2, and pim‐3, all of which are reported to be overexpressed in several hematologic malignancies 1 . Several pathways and molecules involved in tumor progression, such as the well‐known interleukin (IL)‐6/STAT3 and TNF/NF‐κB pathways, have recently been found to be involved in the transcription of pim kinases as well 2 . Targeting these pathways would inhibit myeloma cell proliferation by promoting cell cycle arrest and activating metabolic pathways, such as glycolysis and lipid biosynthesis 3 .…”

Section: Introductionmentioning

confidence: 99%

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An overview of pim kinase as a target in multiple myeloma

et al. 2023

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Multiple myeloma (MM) is the second common hematologic malignancy manifesting as a clonal proliferation of plasma cells in the bone marrow. In recent years, high expression and activity of pim kinase have been found to be associated with both the progression and prognosis of a significant proportion of malignant diseases. Therefore, pim kinase has become a potential therapeutic target in the treatment of MM and some pim kinase inhibitors have demonstrated good efficacy in clinical trials. Based on nearly the entire literature searched from PubMed in the field of pim kinase in MM, the paper concluded how pim kinase got involved in the proliferation of myeloma cells, the progression of bone disease infiltration, and even in the regulation of the immune microenvironment. Next as a very promising drug, the effectiveness of pim kinase inhibitors as single agents or in combination with other drugs in the treatment of MM was also summarized. Our analysis will guide the clinical use of pim kinase inhibitors for managing tumor load and bone disease in MM patients.

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Section: Clinical Efficacy Of Pim Kinase Inhibitors In MMsupporting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

An overview of pim kinase as a target in multiple myeloma

et al. 2023

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“…The up-regulation of PIM family member, PIM1/2/3 , was observed in CD8-GNLY effector T cells, NK-FCGR3A-CCL3, cDC-CD1C-AREG and monocyte-FCGR3A. More and more studies demonstrated PIM kinases are constitutively active serine/threonine kinases that play important roles in hematological malignancies ( 52 ), including MM ( 53 ). Inhibition of PIM kinase displayed significant anti-tumor efficacy in MM ( 54 ).…”

Section: Discussionmentioning

confidence: 99%

Aberrant metabolic processes promote the immunosuppressive microenvironment in multiple myeloma

Sun

Gong

et al. 2022

Front. Immunol.

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IntroductionMultiple myeloma (MM) is still an incurable plasma cell malignancy. The efficacy of immunotherapy on MM remains unsatisfactory, and the underlying molecular mechanisms still are not fully understood.MethodsIn this study, we delineated the dynamic features of immune cell in MM bone marrow (BM) along with elevated tumor cell infiltration by single-cell RNA sequencing (scRNA-seq), and investigated the underlying mechanisms on dysfunction of immune cells associated with myelomagenesis.ResultsWe found that immune cells were activated in those patients with low infiltration of tumor cells, meanwhile suppressed with elevated infiltration of MM cells, which facilitated MM escaping from immune surveillance. Besides PD-1, abnormal expression of PIM kinases, KLRB1 and KLRC1 were involved in the defect of immune cells in MM patients. Importantly, we found aberrant metabolic processes were associated with the immunosuppressive microenvironment in MM patients. Disordered amino acid metabolism promoted the dysfunction of cytotoxicity CD8 T cells as well as lipid metabolism disorder was associated with the dysregulation of NK and DCs in MM. As metabolic checkpoints, PIM kinases would be potential effective strategies for MM immunotherapy.DiscussionIn summary, redressing the disordered metabolism should be the key points to get promising effects in immune-based therapies.

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“…In future research, it is imperative to investigate diverse approaches aimed at improving both the efficacy and tolerability of therapeutic interventions. This may involve dose adjustments, exploration of alternative routes of administration, and optimization of dosing intervals to discover more clinically applicable strategies. − …”

Section: Introductionmentioning

confidence: 99%

Comprehensive Insights that Targeting PIM for Cancer Therapy: Prospects and Obstacles

Chen,

Mao,

Ren

et al. 2024

J. Med. Chem.

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Proviral integration sitea for Moloney-murine leukemia virus (PIM) kinases are a family of highly conserved serine/tyrosine kinases consisting of three members, PIM-1, PIM-2, and PIM-3. These kinases regulate a wide range of substrates through phosphorylation and affect key cellular processes such as transcription, translation, proliferation, apoptosis, and energy metabolism. Several PIM inhibitors are currently undergoing clinical trials, such as a phase I clinical trial of Uzanserti (5) for the treatment of relapsed diffuse large B-cell lymphoma that has been completed. The current focus encompasses the structural and biological characterization of PIM, ongoing research progress on small-molecule inhibitors undergoing clinical trials, and evaluation analysis of persisting challenges in this field. Additionally, the design and discovery of small-molecule inhibitors targeting PIM in recent years have been explored, with a particular emphasis on medicinal chemistry, aiming to provide valuable insights for the future development of PIM inhibitors. ■ SIGNIFICANCEA concise summary of research in the field of PIM inhibition for cancer, with a focus on medicinal chemistry, is presented. An analysis of current compounds entering clinical trials highlights existing issues and provides viewpoints on potential solutions. Future prospects and recommendations for development are discussed, emphasizing the need for unique perspectives and analyses in medicinal chemistry to stimulate critical thinking, expand understanding, and advance research in this field.

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PIM Kinases in Multiple Myeloma

Cited by 18 publications

References 88 publications

An overview of pim kinase as a target in multiple myeloma

An overview of pim kinase as a target in multiple myeloma

Aberrant metabolic processes promote the immunosuppressive microenvironment in multiple myeloma

Comprehensive Insights that Targeting PIM for Cancer Therapy: Prospects and Obstacles

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