Title:Targeted Inhibition of the PI3K/Akt/mTOR Signaling Axis: Potential for
Sarcoma Therapy
Volume: 24
Issue: 16
Author(s): Atif Khurshid Wani, Reena Singh, Nahid Akhtar, Ajit Prakash, Eugenie Nepovimova, Patrik Oleksak, Zofia Chrienova, Suliman Alomar, Chirag Chopra*Kamil Kuca*
Affiliation:
- School of Bioengineering and Biosciences, Lovely Professional University, Jalandhar (144411), Punjab, India
- Department
of Chemistry, Faculty of Science, University of Hradec Králové, Hradec Králové, Czechia
- Biomedical Research Center, University Hospital
Hradec Kralove, Hradec Králové, Czechia
Keywords:
Sarcoma, biomarkers, FDA approved drugs, PI3K/Akt/mToR inhibitors, phytochemicals, nanomaterials.
Abstract: Sarcoma is a heterogeneous group of malignancies often resistant to conventional chemotherapy
and radiation therapy. The phosphatidylinositol-3-kinase/ protein kinase B /mammalian target
of rapamycin (PI3K/Akt/mTOR) signaling pathway has emerged as a critical cancer target due
to its central role in regulating key cellular processes such as cell growth, proliferation, survival, and
metabolism. Dysregulation of this pathway has been implicated in the development and progression
of bone sarcomas (BS) and soft tissue sarcomas (STS). PI3K/Akt/mTOR inhibitors have shown
promising preclinical and clinical activity in various cancers. These agents can inhibit the activation
of PI3K, Akt, and mTOR, thereby reducing the downstream signaling events that promote tumor
growth and survival. In addition, PI3K/Akt/mTOR inhibitors have been shown to enhance the efficacy
of other anticancer therapies, such as chemotherapy and radiation therapy. The different types
of PI3K/Akt/mTOR inhibitors vary in their specificity, potency, and side effect profiles and may be
effective depending on the specific sarcoma type and stage. The molecular targeting of
PI3K/Akt/mToR pathway using drugs, phytochemicals, nanomaterials (NMs), and microbe-derived
molecules as Pan-PI3K inhibitors, selective PI3K inhibitors, and dual PI3K/mTOR inhibitors have
been delineated. While there are still challenges to be addressed, the preclinical and clinical evidence
suggests that these inhibitors may significantly improve patient outcomes. Further research is
needed to understand the potential of these inhibitors as sarcoma therapeutics and to continue developing
more selective and effective agents to meet the clinical needs of sarcoma patients.
