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Review
. 2024 Aug:46:102023.
doi: 10.1016/j.tranon.2024.102023. Epub 2024 Jun 8.

Inhibition of STAT3: A promising approach to enhancing the efficacy of chemotherapy in medulloblastoma

Sachindra Kumar  1 , Dube Aakash Arwind  2 , Harish Kumar B  1 , Samyak Pandey  1 , Raksha Nayak  1 , Megh Pravin Vithalkar  1 , Nitesh Kumar  2 , K Sreedhara Ranganath Pai  3
Affiliations
Review

Inhibition of STAT3: A promising approach to enhancing the efficacy of chemotherapy in medulloblastoma

Sachindra Kumar et al. Transl Oncol. 2024 Aug.

Abstract

Medulloblastoma is a type of brain cancer that primarily affects children. While chemotherapy has been shown to be effective in treating medulloblastoma, the development of chemotherapy resistance remains a challenge. One potential therapeutic approach is to selectively inhibit the inducible transcription factor called STAT3, which is known to play a crucial role in the survival and growth of tumor cells. The activation of STAT3 has been linked to the growth and progression of various cancers, including medulloblastoma. Inhibition of STAT3 has been shown to sensitize medulloblastoma cells to chemotherapy, leading to improved treatment outcomes. Different approaches to STAT3 inhibition have been developed, including small-molecule inhibitors and RNA interference. Preclinical studies have shown the efficacy of STAT3 inhibitors in medulloblastoma, and clinical trials are currently ongoing to evaluate their safety and effectiveness in patients with various solid tumors, including medulloblastoma. In addition, researchers are also exploring ways to optimize the use of STAT3 inhibitors in combination with chemotherapy and identify biomarkers that can predict treatment that will help to develop personalized treatment strategies. This review highlights the potential of selective inhibition of STAT3 as a novel approach for the treatment of medulloblastoma and suggests that further research into the development of STAT3 inhibitors could lead to improved outcomes for patients with aggressive cancer.

Keywords: Cancer; Chemotherapy resistance; Medulloblastoma; STAT3 inhibitors; Targeted therapy.

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Conflict of interest statement

Declaration of competing interest The authors declare no conflicts of interest.

Figures

Image, graphical abstract
Graphical abstract
Fig 1
Fig. 1
Structural organization of STAT3 [161].
Fig 2
Fig. 2
(A) This diagram illustrates the mechanism of STAT3. Upon cytokine stimulation, JAK activates STAT3 through phosphorylation. Phosphorylated STAT3 forms dimers and translocates to the nucleus, initiating specific gene expression. (B) Binding site. (C) Interaction with ligand.
Fig 3
Fig. 3
Mechanisms by which STAT3 inhibitors act on medulloblastoma [162].
Fig 4
Fig. 4
Workflow for exosome-based strategy used for STAT3 inhibition.
See this image and copyright information in PMC

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