Development of PI3K inhibitors: lessons learned from early clinical trials View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2013-03

AUTHORS

Jordi Rodon, Rodrigo Dienstmann, Violeta Serra, Josep Tabernero

ABSTRACT

The phosphatidylinositol 3-kinase (PI3K) pathway has an important role in cell metabolism, growth, migration, survival and angiogenesis. Drug development aimed at targetable genetic aberrations in the PI3K/AKT/mTOR pathway has been fomented by observations that alterations in this pathway induce tumour formation and that inappropriate PI3K signalling is a frequent occurrence in human cancer. Many of the agents developed have been evaluated in early stage clinical trials. This Review focuses on early clinical and translational data related to inhibitors of the PI3K/AKT/mTOR pathway, as these data will likely guide the further clinical development of such agents. We review data from those trials, delineating the safety profile of the agents--whether observed sequelae could be mechanism-based or off-target effects--and drug efficacy. We describe predictive biomarkers explored in clinical trials and preclinical mechanisms of resistance. We also discuss key unresolved translational questions related to the clinical development of inhibitors of the PI3K/AKT/mTOR pathway and propose designs for biomarker-driven trials to address those issues. More... »

PAGES

143

References to SciGraph publications

  • 2006-10. The skin and hair as surrogate tissues for measuring the target effect of inhibitors of phosphoinositide-3-kinase signaling in CANCER CHEMOTHERAPY AND PHARMACOLOGY
  • 2011-09. Oncogenic PIK3CA-driven mammary tumors frequently recur via PI3K pathway–dependent and PI3K pathway–independent mechanisms in NATURE MEDICINE
  • 2012-06. Molecular prescreening to select patient population in early clinical trials in NATURE REVIEWS CLINICAL ONCOLOGY
  • 2010-07-01. Clinical Development of Phosphatidylinositol-3 Kinase Pathway Inhibitors in PHOSPHOINOSITIDE 3-KINASE IN HEALTH AND DISEASE
  • 2011-11. A chemical-genetic screen reveals a mechanism of resistance to PI3K inhibitors in cancer in NATURE CHEMICAL BIOLOGY
  • 2010-09. Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma in NATURE
  • 2006-05. Critical role for the p110α phosphoinositide-3-OH kinase in growth and metabolic regulation in NATURE
  • 2012-06. β-catenin confers resistance to PI3K and AKT inhibitors and subverts FOXO3a to promote metastasis in colon cancer in NATURE MEDICINE
  • 2008-10-23. Comprehensive genomic characterization defines human glioblastoma genes and core pathways in NATURE
  • 2012-07. Comprehensive molecular characterization of human colon and rectal cancer in NATURE
  • 2011-07. PIK3CA mutation, but not PTEN loss of function, determines the sensitivity of breast cancer cells to mTOR inhibitory drugs in ONCOGENE
  • 2008-12. Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers in NATURE MEDICINE
  • 2012-12. Clinical development of phosphatidylinositol 3-kinase inhibitors for cancer treatment in BMC MEDICINE
  • 2011-12. Mutations in the phosphatidylinositol 3-kinase pathway: role in tumor progression and therapeutic implications in breast cancer in BREAST CANCER RESEARCH
  • 2011-02. Regulation of cancer cell metabolism in NATURE REVIEWS CANCER
  • 2006-08. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism in NATURE REVIEWS GENETICS
  • 2011-06-29. Integrated genomic analyses of ovarian carcinoma in NATURE
  • 2011-06. PI3K inhibition results in enhanced HER signaling and acquired ERK dependency in HER2-overexpressing breast cancer in ONCOGENE
  • 2012-06. Sequence analysis of mutations and translocations across breast cancer subtypes in NATURE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nrclinonc.2013.10

    DOI

    http://dx.doi.org/10.1038/nrclinonc.2013.10

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1031948211

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/23400000


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