PI3K/AKT/mTOR pathway in multiple myeloma: from basic biology to clinical promise

Area of Science:

• Hematology
• Oncology
• Molecular Biology

Background:

• Multiple myeloma (MM) is the second most common hematological malignancy, arising from terminally differentiated plasma cells.
• MM cells accumulate in the bone marrow, interacting closely with the marrow microenvironment, which promotes cell survival.
• Genomic alterations and microenvironmental interactions contribute to MM pathophysiology.

Purpose of the Study:

• To review the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway.
• To elucidate the role of the PI3K/AKT/mTOR pathway in Multiple Myeloma (MM).
• To discuss preclinical and clinical findings of targeting this pathway in MM.

Main Methods:

• Literature review of the PI3K/AKT/mTOR pathway in MM.
• Analysis of preclinical data on PI3K/AKT/mTOR inhibitors.
• Evaluation of clinical trial data for drugs targeting this pathway in MM.

Main Results:

• The PI3K/AKT/mTOR pathway is aberrantly activated in a significant proportion of MM patients.
• This pathway activation enhances MM cell survival and can contribute to therapeutic resistance.
• Promising preclinical results have been observed for drugs targeting the PI3K/AKT/mTOR pathway.

Conclusions:

• The PI3K/AKT/mTOR pathway is a central player in MM pathophysiology.
• Targeting the PI3K/AKT/mTOR pathway represents a promising therapeutic strategy for MM.
• Further clinical investigation of PI3K/AKT/mTOR inhibitors in MM is warranted.