Mammalian target of rapamycin

Funda Meric-Bernstam, Gordon Mills

Research output: Contribution to journalReview article

28 Citations (Scopus)

Abstract

Targeted molecular therapeutics are tailored toward the genetic abnormalities that cause tumor progression. Modulation of certain signaling pathways that are aberrant in cancer cells has the potential to provide an effective, nontoxic approach to therapy in a broad range of cancers. Agents targeting BCR-ABL (imatinib mesylate [formerly known as STI-571], Gleevec; Novartis Pharmaceuticals Corp, East Hanover, NJ), retinoid receptor fusion proteins (all-trans retinoic acid), ErbB-2 or HER2/neu (trastuzumab, Herceptin; Genentech, Inc, South San Francisco, CA), epidermal growth factor receptor (IMC-C225 and ZD1839), and the phosphatidylinositol 3-kinase pathway (CCI-779) have all induced remarkable, nontoxic responses in a subset of patients with cancer and abnormalities in the corresponding signal transduction cascades. To achieve successful individualized therapy, the specific components within the aberrant signaling pathways that are driving the pathophysiology of the tumors must be identified in each patient. Molecular diagnostics can identify patients in whom the target is aberrant; linking molecular diagnostics with effective molecular therapeutics will be necessary to translate these concepts into approaches that will alter the outcome for patients with cancer. In addition, intermediary markers and/or molecular imaging techniques must be used to identify the biologically relevant dose that is sufficient to inhibit the target of interest. This review focuses on the PI3K pathway, and novel molecules targeting this pathway, to illustrate the questions and challenges underlying the implementation of molecular therapeutics in breast and ovarian cancer.

Original languageEnglish (US)
Pages (from-to)10-17
Number of pages8
JournalSeminars in Oncology
Volume31
Issue numberSUPPL. 16
DOIs
StatePublished - Dec 1 2004
Externally publishedYes

Fingerprint

Sirolimus
Neoplasms
Molecular Pathology
Phosphatidylinositol 3-Kinase
Therapeutics
Molecular Imaging
San Francisco
Retinoids
Tretinoin
Phosphatidylinositol 3-Kinases
Epidermal Growth Factor Receptor
Ovarian Neoplasms
Signal Transduction
Breast Neoplasms
Pharmaceutical Preparations
Imatinib Mesylate
Proteins

ASJC Scopus subject areas

  • Oncology

Cite this

Mammalian target of rapamycin. / Meric-Bernstam, Funda; Mills, Gordon.

In: Seminars in Oncology, Vol. 31, No. SUPPL. 16, 01.12.2004, p. 10-17.

Research output: Contribution to journalReview article

Meric-Bernstam, Funda ; Mills, Gordon. / Mammalian target of rapamycin. In: Seminars in Oncology. 2004 ; Vol. 31, No. SUPPL. 16. pp. 10-17.
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