Targeting PI3K-AKT Pathway for Cancer Therapy

Yiling Lu, Hongwei Wang, Gordon Mills

Research output: Contribution to journalReview article

72 Citations (Scopus)

Abstract

The phosphatidilinositol 3-kinase/protein kinase B (PI3K-AKT) pathway presents an exciting new target for molecular therapeutics. While exhibiting great promise, additional preclinical and clinical studies will be required to determine how best to target this pathway to improve patient outcome. A number of questions need to be answered prior to the implementation into patient care practices. As described below, the PI3K-AKT pathway regulates a broad spectrum of cellular processes, some of which are necessary to maintain normal physiological functions, which potentially contribute to the toxicity of the drugs targeting the pathway. Elucidation of the precise function of the PI3K-AKT isoforms, could promote the development of isoform specific approaches to provide a selective action on tumor cells. However, whether this will be possible due to conservation of structural domains is not yet clear. Inhibition of the PI3K-AKT pathway at multiple sites or a combination with inhibitors of different signaling pathways may allow the development of an acceptable therapeutic index for cancer management. Further, inhibition of the PI3K-AKT pathway combined with conventional chemotherapy or radiation therapy may provide a more effective strategy to improve patient outcome. As molecular therapeutics target the underlying defects in patient tumors, molecular diagnostics are required to identify patients with particular genetic aberrations in the pathway. It will be critical to provide adequate therapeutic strategies tailored to each patient. In addition, patients with different genetic backgrounds or in different health conditions could respond adversely to particular therapeutics. Therefore, identification of patients for particular drugs based on the underlying genetic defects in the tumor as well as the characteristics of the host would be of benefit for improving patient outcome. Linking the targeted therapeutics to molecular imaging approaches will determine appropriate biologically relevant dose for patients. It will also define expected tumor responsiveness and eventually will improve efficacy and decrease toxicity. In this regard, personalized molecular medicine is likely to soon provide effective cancer treatment.

Original languageEnglish (US)
Pages (from-to)205-228
Number of pages24
JournalReviews in Clinical and Experimental Hematology
Volume7
Issue number2
StatePublished - Jun 1 2003
Externally publishedYes

Fingerprint

Phosphatidylinositol 3-Kinases
Neoplasms
Therapeutics
Protein Isoforms
Molecular Medicine
Proto-Oncogene Proteins c-akt
Precision Medicine
Molecular Imaging
Molecular Pathology
Drug Delivery Systems
Patient Care
Phosphotransferases
Radiotherapy
Drug Therapy
Health
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Hematology

Cite this

Targeting PI3K-AKT Pathway for Cancer Therapy. / Lu, Yiling; Wang, Hongwei; Mills, Gordon.

In: Reviews in Clinical and Experimental Hematology, Vol. 7, No. 2, 01.06.2003, p. 205-228.

Research output: Contribution to journalReview article

Lu, Yiling ; Wang, Hongwei ; Mills, Gordon. / Targeting PI3K-AKT Pathway for Cancer Therapy. In: Reviews in Clinical and Experimental Hematology. 2003 ; Vol. 7, No. 2. pp. 205-228.
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