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  1. Article ; Online: The present and future of PI3K inhibitors for cancer therapy.

    Castel, Pau / Toska, Eneda / Engelman, Jeffrey A / Scaltriti, Maurizio

    Nature cancer

    2021  Volume 2, Issue 6, Page(s) 587–597

    Abstract: Phosphoinositide-3- kinase (PI3K) signaling regulates cellular proliferation, survival and metabolism, and its aberrant activation is one of the most frequent oncogenic events across human cancers. In the last few decades, research focused on the ... ...

    Abstract Phosphoinositide-3- kinase (PI3K) signaling regulates cellular proliferation, survival and metabolism, and its aberrant activation is one of the most frequent oncogenic events across human cancers. In the last few decades, research focused on the development of PI3K inhibitors, from preclinical tool compounds to the highly specific medicines approved to treat patients with cancer. Herein we discuss current paradigms for PI3K inhibitors in cancer therapy, focusing on clinical data and mechanisms of action. We also discuss current limitations in the use of PI3K inhibitors including toxicities and mechanisms of resistance, with specific emphasis on approaches aimed to improve their efficacy.
    MeSH term(s) Humans ; Neoplasms/drug therapy ; Phosphatidylinositol 3-Kinase/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphoinositide-3 Kinase Inhibitors/therapeutic use ; Signal Transduction
    Chemical Substances Phosphoinositide-3 Kinase Inhibitors ; Phosphatidylinositol 3-Kinase (EC 2.7.1.137)
    Language English
    Publishing date 2021-06-17
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2662-1347
    ISSN (online) 2662-1347
    DOI 10.1038/s43018-021-00218-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Crizotinib Resensitization by Compound Mutation.

    Shaw, Alice T / Engelman, Jeffrey A

    The New England journal of medicine

    2016  Volume 374, Issue 18, Page(s) 1790–1791

    MeSH term(s) Carcinoma, Non-Small-Cell Lung/drug therapy ; Drug Resistance, Neoplasm/genetics ; Female ; Humans ; Lactams, Macrocyclic/therapeutic use ; Lung Neoplasms/drug therapy ; Mutation ; Protein Kinase Inhibitors/therapeutic use ; Pyrazoles/therapeutic use ; Pyridines/therapeutic use ; Receptor Protein-Tyrosine Kinases/genetics
    Chemical Substances Lactams, Macrocyclic ; Protein Kinase Inhibitors ; Pyrazoles ; Pyridines ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1)
    Language English
    Publishing date 2016-05-05
    Publishing country United States
    Document type Comment ; Letter
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMc1601366
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  3. Article ; Online: Distinct evolutionary paths to TKI resistance in NSCLC.

    Niederst, Matthew J / Engelman, Jeffrey A / Hata, Aaron N

    Cell cycle (Georgetown, Tex.)

    2018  Volume 17, Issue 3, Page(s) 298–299

    MeSH term(s) Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/pathology ; Drug Resistance, Neoplasm ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/pathology ; Neoplasm, Residual/pathology ; Protein Kinase Inhibitors/therapeutic use
    Chemical Substances Antineoplastic Agents ; Protein Kinase Inhibitors
    Language English
    Publishing date 2018-01-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2146183-1
    ISSN 1551-4005 ; 1538-4101 ; 1554-8627
    ISSN (online) 1551-4005
    ISSN 1538-4101 ; 1554-8627
    DOI 10.1080/15384101.2016.1221024
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  4. Article ; Online: The double life of p85.

    Costa, Carlotta / Engelman, Jeffrey A

    Cancer cell

    2014  Volume 26, Issue 4, Page(s) 445–447

    Abstract: A growing number of mutations in PIK3R1, the gene that encodes for the p85α regulatory subunit of PI3K, have been recently identified. In this issue of Cancer Cell, Cheung and colleagues describe two neomorphic PIK3R1 mutants prevalent in endometrial and ...

    Abstract A growing number of mutations in PIK3R1, the gene that encodes for the p85α regulatory subunit of PI3K, have been recently identified. In this issue of Cancer Cell, Cheung and colleagues describe two neomorphic PIK3R1 mutants prevalent in endometrial and colon cancer that induce transformation via activation of PI3K-independent pathways.
    MeSH term(s) Colonic Neoplasms/genetics ; Endometrial Neoplasms/genetics ; Female ; Humans ; Mutation ; Phosphatidylinositol 3-Kinases/genetics ; Phosphatidylinositol 3-Kinases/physiology
    Chemical Substances PIK3R1 protein, human (EC 2.7.1.-) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-)
    Language English
    Publishing date 2014-10-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2078448-X
    ISSN 1878-3686 ; 1535-6108
    ISSN (online) 1878-3686
    ISSN 1535-6108
    DOI 10.1016/j.ccell.2014.09.011
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  5. Article ; Online: Ceritinib in ALK-rearranged non-small-cell lung cancer.

    Shaw, Alice T / Engelman, Jeffrey A

    The New England journal of medicine

    2014  Volume 370, Issue 26, Page(s) 2537–2539

    MeSH term(s) Carcinoma, Non-Small-Cell Lung/drug therapy ; Drug Resistance, Neoplasm/genetics ; Female ; Humans ; Lung Neoplasms/drug therapy ; Male ; Protein Kinase Inhibitors/administration & dosage ; Pyrimidines/administration & dosage ; Receptor Protein-Tyrosine Kinases/genetics ; Sulfones/administration & dosage
    Chemical Substances Protein Kinase Inhibitors ; Pyrimidines ; Sulfones ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1)
    Language English
    Publishing date 2014-06-26
    Publishing country United States
    Document type Comment ; Letter
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMc1404894
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  6. Article ; Online: Targeting PI3K signalling in cancer: opportunities, challenges and limitations.

    Engelman, Jeffrey A

    Nature reviews. Cancer

    2009  Volume 9, Issue 8, Page(s) 550–562

    Abstract: There are ample genetic and laboratory studies that suggest the PI3K-Akt pathway is vital to the growth and survival of cancer cells. Inhibitors targeting this pathway are entering the clinic at a rapid pace. In this Review, the therapeutic potential of ... ...

    Abstract There are ample genetic and laboratory studies that suggest the PI3K-Akt pathway is vital to the growth and survival of cancer cells. Inhibitors targeting this pathway are entering the clinic at a rapid pace. In this Review, the therapeutic potential of drugs targeting PI3K-Akt signalling for the treatment of cancer is discussed. I focus on the advantages and drawbacks of different treatment strategies for targeting this pathway, the cancers that might respond best to these therapies and the challenges and limitations that confront their clinical development.
    MeSH term(s) Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Humans ; Neoplasms/drug therapy ; Neoplasms/etiology ; Neoplasms/pathology ; Phosphatidylinositol 3-Kinases/physiology ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Protein Kinases/physiology ; Proto-Oncogene Proteins c-akt/physiology ; Signal Transduction/drug effects ; Signal Transduction/physiology ; TOR Serine-Threonine Kinases
    Chemical Substances Antineoplastic Agents ; Protein Kinase Inhibitors ; Protein Kinases (EC 2.7.-) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; MTOR protein, human (EC 2.7.1.1) ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
    Language English
    Publishing date 2009-02-19
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2062767-1
    ISSN 1474-1768 ; 1474-175X
    ISSN (online) 1474-1768
    ISSN 1474-175X
    DOI 10.1038/nrc2664
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  7. Article ; Online: Retraction Note: EGFR and MET receptor tyrosine kinase-altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers.

    Garofalo, Michela / Romano, Giulia / Di Leva, Gianpiero / Nuovo, Gerard / Jeon, Young-Jun / Ngankeu, Apollinaire / Sun, Jin / Lovat, Francesca / Alder, Hansjuerg / Condorelli, Gerolama / Engelman, Jeffrey A / Ono, Mayumi / Rho, Jin Kyung / Cascione, Luciano / Volinia, Stefano / Nephew, Kenneth P / Croce, Carlo M

    Nature medicine

    2022  Volume 28, Issue 11, Page(s) 2436

    Language English
    Publishing date 2022-10-04
    Publishing country United States
    Document type Retraction of Publication
    ZDB-ID 1220066-9
    ISSN 1546-170X ; 1078-8956
    ISSN (online) 1546-170X
    ISSN 1078-8956
    DOI 10.1038/s41591-022-02044-2
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    Zs.A 4212: Show issues Location:
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  8. Article ; Online: ERBB receptors: from oncogene discovery to basic science to mechanism-based cancer therapeutics.

    Arteaga, Carlos L / Engelman, Jeffrey A

    Cancer cell

    2014  Volume 25, Issue 3, Page(s) 282–303

    Abstract: ERBB receptors were linked to human cancer pathogenesis approximately three decades ago. Biomedical investigators have since developed substantial understanding of the biology underlying the dependence of cancers on aberrant ERBB receptor signaling. An ... ...

    Abstract ERBB receptors were linked to human cancer pathogenesis approximately three decades ago. Biomedical investigators have since developed substantial understanding of the biology underlying the dependence of cancers on aberrant ERBB receptor signaling. An array of cancer-associated genetic alterations in ERBB receptors has also been identified. These findings have led to the discovery and development of mechanism-based therapies targeting ERBB receptors that have improved outcome for many cancer patients. In this Perspective, we discuss current paradigms of targeting ERBB receptors with cancer therapeutics and our understanding of mechanisms of action and resistance to these drugs. As current strategies still have limitations, we also discuss challenges and opportunities that lie ahead as basic scientists and clinical investigators work toward more breakthroughs.
    MeSH term(s) Animals ; Antibodies, Monoclonal, Humanized/therapeutic use ; Drug Resistance, Neoplasm/genetics ; ErbB Receptors/antagonists & inhibitors ; ErbB Receptors/genetics ; ErbB Receptors/metabolism ; Humans ; Mice ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/metabolism ; Receptor, ErbB-2/antagonists & inhibitors ; Receptor, ErbB-2/genetics ; Receptor, ErbB-2/metabolism ; Receptor, ErbB-3/genetics ; Receptor, ErbB-3/metabolism ; Receptor, ErbB-4 ; Signal Transduction
    Chemical Substances Antibodies, Monoclonal, Humanized ; EGFR protein, human (EC 2.7.10.1) ; ERBB2 protein, human (EC 2.7.10.1) ; ERBB3 protein, human (EC 2.7.10.1) ; ERBB4 protein, human (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1) ; Erbb4 protein, mouse (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1) ; Receptor, ErbB-3 (EC 2.7.10.1) ; Receptor, ErbB-4 (EC 2.7.10.1)
    Language English
    Publishing date 2014-03-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2078448-X
    ISSN 1878-3686 ; 1535-6108
    ISSN (online) 1878-3686
    ISSN 1535-6108
    DOI 10.1016/j.ccr.2014.02.025
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  9. Article ; Online: SnapShot: non-small cell lung cancer.

    Heist, Rebecca S / Engelman, Jeffrey A

    Cancer cell

    2012  Volume 21, Issue 3, Page(s) 448.e2

    MeSH term(s) Carcinoma, Non-Small-Cell Lung/genetics ; Humans ; Lung Neoplasms/genetics ; Neoplasm Proteins/genetics ; Neoplasm Proteins/physiology
    Chemical Substances Neoplasm Proteins
    Language English
    Publishing date 2012-03-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2078448-X
    ISSN 1878-3686 ; 1535-6108
    ISSN (online) 1878-3686
    ISSN 1535-6108
    DOI 10.1016/j.ccr.2012.03.007
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  10. Article: The role of phosphoinositide 3-kinase pathway inhibitors in the treatment of lung cancer.

    Engelman, Jeffrey A

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2007  Volume 13, Issue 15 Pt 2, Page(s) s4637–40

    Abstract: The phosphoinositide 3-kinase signaling network is widely implicated in the pathogenesis of human cancer. This pathway is commandeered by cancer cells to promote unrestrained cellular growth and survival. In this brief review, we speculate about the uses ...

    Abstract The phosphoinositide 3-kinase signaling network is widely implicated in the pathogenesis of human cancer. This pathway is commandeered by cancer cells to promote unrestrained cellular growth and survival. In this brief review, we speculate about the uses of inhibitors of phosphoinositide 3-kinase signaling as treatments for human cancers, with an emphasis on non-small cell lung cancer.
    MeSH term(s) Animals ; Antineoplastic Agents/therapeutic use ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Humans ; Lung Neoplasms/drug therapy ; Phosphatidylinositol 3-Kinases/antagonists & inhibitors ; Protein Kinase Inhibitors/therapeutic use
    Chemical Substances Antineoplastic Agents ; Protein Kinase Inhibitors ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-)
    Language English
    Publishing date 2007-08-01
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-07-0653
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