Phenotypic screening in cancer drug discovery — past, present and future

Identification and Characterization of a Novel Chemotype MEK Inhibitor Able to Alter the Phosphorylation State of MEK1/2

(2015) Takayuki Yoshida et al.   Oncotarget

From Anecdote to Targeted Therapy: The Curious Case of Thalidomide in Multiple Myeloma

(2014) Jonathan D. Licht et al.   CANCER CELL

Novel anti-glioblastoma agents and therapeutic combinations identified from a collection of FDA approved drugs

(2014) Pengfei Jiang et al.   Journal of Translational Medicine

A phase I/II study of sepantronium bromide (YM155, survivin suppressor) with paclitaxel and carboplatin in patients with advanced non-small-cell lung cancer

(2013) R. J. Kelly et al.   ANNALS OF ONCOLOGY

Development of Multiple Cell-Based Assays for the Detection of Histone H3 Lys27 Trimethylation (H3K27me3)

(2013) Jie Qian et al.   ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES

OPB-31121, a novel small molecular inhibitor, disrupts the JAK2/STAT3 pathway and exhibits an antitumor activity in gastric cancer cells

(2013) Mi-Jung Kim et al.   CANCER LETTERS

Cytotoxic Activity of Tivantinib (ARQ 197) Is Not Due Solely to c-MET Inhibition

(2013) R. Katayama et al.   CANCER RESEARCH

Treat cancers by targeting survivin: Just a dream or future reality?

(2013) Mohane Selvaraj Coumar et al.   CANCER TREATMENT REVIEWS

Lessons from the Cancer Genome

(2013) Levi A. Garraway et al.   CELL

Tivantinib (ARQ197) Displays Cytotoxic Activity That Is Independent of Its Ability to Bind MET

(2013) C. Basilico et al.   CLINICAL CANCER RESEARCH

Inhibition of BET Bromodomain Targets Genetically Diverse Glioblastoma

(2013) Z. Cheng et al.   CLINICAL CANCER RESEARCH

Phenotypic vs. Target-Based Drug Discovery for First-in-Class Medicines

(2013) D C Swinney   CLINICAL PHARMACOLOGY & THERAPEUTICS

Discontinued drugs in 2012: oncology drugs

(2013) Robert Williams   EXPERT OPINION ON INVESTIGATIONAL DRUGS

Personalizing Oncology: Perspectives and Prospects

(2013) John Mendelsohn   JOURNAL OF CLINICAL ONCOLOGY

Phase I study of ON 01910.Na (Rigosertib), a multikinase PI3K inhibitor in relapsed/refractory B-cell malignancies

(2013) M Roschewski et al.   LEUKEMIA

Tivantinib—a cytotoxic drug in MET inhibitor's clothes?

(2013) Paolo Michieli et al.   Nature Reviews Clinical Oncology

Cooperativity between MAPK and PI3K signaling activation is required for glioblastoma pathogenesis

(2013) M. Vitucci et al.   NEURO-ONCOLOGY

Thalidomide-analogue biology: immunological, molecular and epigenetic targets in cancer therapy

(2013) J Shortt et al.   ONCOGENE

A Simple High-Content Cell Cycle Assay Reveals Frequent Discrepancies between Cell Number and ATP and MTS Proliferation Assays

(2013) Grace Ka Yan Chan et al.   PLoS One

Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics

(2013) A. Sottoriva et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Lung cancer-initiating cells: a novel target for cancer therapy

(2013) Brian J. Morrison et al.   Targeted Oncology

A novel STAT inhibitor, OPB-31121, has a significant antitumor effect on leukemia with STAT-addictive oncokinases

(2013) F Hayakawa et al.   Blood Cancer Journal

Patient-Specific Orthotopic Glioblastoma Xenograft Models Recapitulate the Histopathology and Biology of Human Glioblastomas In Situ

(2013) Kyeung Min Joo et al.   Cell Reports

The “survivin suppressants” NSC 80467 and YM155 induce a DNA damage response

(2012) Trevor G. Glaros et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

Liver tumor-initiating cells as a therapeutic target for hepatocellular carcinoma

(2012) Terence Kin Wah Lee et al.   CANCER LETTERS

Tasquinimod Is an Allosteric Modulator of HDAC4 Survival Signaling within the Compromised Cancer Microenvironment

(2012) J. T. Isaacs et al.   CANCER RESEARCH

Cancer Stem Cells: Current Status and Evolving Complexities

(2012) Jane E. Visvader et al.   Cell Stem Cell

ON 01910.Na Is Selectively Cytotoxic for Chronic Lymphocytic Leukemia Cells through a Dual Mechanism of Action Involving PI3K/AKT Inhibition and Induction of Oxidative Stress

(2012) C. M. Chapman et al.   CLINICAL CANCER RESEARCH

Lurbinectedin (PM01183), a New DNA Minor Groove Binder, Inhibits Growth of Orthotopic Primary Graft of Cisplatin-Resistant Epithelial Ovarian Cancer

(2012) A. Vidal et al.   CLINICAL CANCER RESEARCH

Bridging the Gap between Preclinical and Clinical Studies Using Pharmacokinetic-Pharmacodynamic Modeling: An Analysis of GDC-0973, a MEK Inhibitor

(2012) H. Wong et al.   CLINICAL CANCER RESEARCH

Antitumor Activity of Targeted and Cytotoxic Agents in Murine Subcutaneous Tumor Models Correlates with Clinical Response

(2012) H. Wong et al.   CLINICAL CANCER RESEARCH

Is poor research the cause of the declining productivity of the pharmaceutical industry? An industry in need of a paradigm shift

(2012) Frank Sams-Dodd   DRUG DISCOVERY TODAY

The multicellular tumor spheroid model for high-throughput cancer drug discovery

(2012) Daniel V LaBarbera et al.   Expert Opinion on Drug Discovery

Sorafenib in melanoma

(2012) Joanna Mangana et al.   EXPERT OPINION ON INVESTIGATIONAL DRUGS

Modern Phenotypic Drug Discovery Is a Viable, Neoclassic Pharma Strategy

(2012) Jonathan A. Lee et al.   JOURNAL OF MEDICINAL CHEMISTRY

Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide

(2012) A Lopez-Girona et al.   LEUKEMIA

Synthetic Lethal Screening with Small-Molecule Inhibitors Provides a Pathway to Rational Combination Therapies for Melanoma

(2012) D. G. Roller et al.   MOLECULAR CANCER THERAPEUTICS

Discovery of small molecule cancer drugs: Successes, challenges and opportunities

(2012) Swen Hoelder et al.   Molecular Oncology

Drug candidates derailed in case of mistaken identity

(2012) Heidi Ledford   NATURE

Raise standards for preclinical cancer research

(2012) C. Glenn Begley et al.   NATURE

A decade of change

(2012) John Arrowsmith   NATURE REVIEWS DRUG DISCOVERY

Epigenetic protein families: a new frontier for drug discovery

(2012) Cheryl H. Arrowsmith et al.   NATURE REVIEWS DRUG DISCOVERY

Vemurafenib: the first drug approved for BRAF-mutant cancer

(2012) Gideon Bollag et al.   NATURE REVIEWS DRUG DISCOVERY

Diagnosing the decline in pharmaceutical R&D efficiency

(2012) Jack W. Scannell et al.   NATURE REVIEWS DRUG DISCOVERY

Anti-Cancer Activity of a Novel Small Molecule Compound That Simultaneously Activates p53 and Inhibits NF-κB Signaling

(2012) Sun Gwan Hwang et al.   PLoS One

Evaluation of Tyrosine Kinase Inhibitor Combinations for Glioblastoma Therapy

(2012) Avadhut D. Joshi et al.   PLoS One

Versatile pathway-centric approach based on high-throughput sequencing to anticancer drug discovery

(2012) H. Li et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Digital transcriptome profiling of normal and glioblastoma-derived neural stem cells identifies genes associated with patient survival

(2012) Pär G Engström et al.   Genome Medicine

Identification and Optimization of Small Molecules That Restore E-Cadherin Expression and Reduce Invasion in Colorectal Carcinoma Cells

(2011) Sydney L. Stoops et al.   ACS Chemical Biology

Micro-ring structures stabilize microdroplets to enable long term spheroid culture in 384 hanging drop array plates

(2011) Amy Y. Hsiao et al.   BIOMEDICAL MICRODEVICES

Development of small-molecule probes that selectively kill cells induced to express mutant RAS

(2011) Michel Weïwer et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Towards automated production and drug sensitivity testing using scaffold-free spherical tumor microtissues

(2011) Maren Drewitz et al.   Biotechnology Journal

Mosaic Amplification of Multiple Receptor Tyrosine Kinase Genes in Glioblastoma

(2011) Matija Snuderl et al.   CANCER CELL

In vitro evaluation of clinical activity and toxicity of anticancer drugs using tumor cells from patients and cells representing normal tissues

(2011) Caroline Haglund et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

Developmental pathways in breast cancer and breast tumor-initiating cells: Therapeutic implications

(2011) Julia Izrailit et al.   CANCER LETTERS

Hallmarks of Cancer: The Next Generation

(2011) Douglas Hanahan et al.   CELL

New tricks from an old drug: A role for quinacrine in anti-cancer therapy?

(2011) Cindy H. Chau et al.   CELL CYCLE

Drug discovery in the next decade: innovation needed ASAP

(2011) Youssef L. Bennani   DRUG DISCOVERY TODAY

Discovery of a Clinical Stage Multi-Kinase Inhibitor Sodium (E)-2-{2-Methoxy-5-[(2′,4′,6′-trimethoxystyrylsulfonyl)methyl]phenylamino}acetate (ON 01910.Na): Synthesis, Structure–Activity Relationship, and Biological Activity

(2011) M. V. Ramana Reddy et al.   JOURNAL OF MEDICINAL CHEMISTRY

Synthesis and Structure−Affinity Relationships of Novel Dibenzylideneacetone Derivatives as Probes for β-Amyloid Plaques

(2011) Mengchao Cui et al.   JOURNAL OF MEDICINAL CHEMISTRY

Targeting the Replication Checkpoint Using SCH 900776, a Potent and Functionally Selective CHK1 Inhibitor Identified via High Content Screening

(2011) T. J. Guzi et al.   MOLECULAR CANCER THERAPEUTICS

In vitro three-dimensional (3D) models in cancer research: An update

(2011) Lauren C. Kimlin et al.   MOLECULAR CARCINOGENESIS

Harnessing synthetic lethal interactions in anticancer drug discovery

(2011) Denise A. Chan et al.   NATURE REVIEWS DRUG DISCOVERY

How were new medicines discovered?

(2011) David C. Swinney et al.   NATURE REVIEWS DRUG DISCOVERY

Believe it or not: how much can we rely on published data on potential drug targets?

(2011) Florian Prinz et al.   NATURE REVIEWS DRUG DISCOVERY

Drug-Tolerant Cancer Cells Show Reduced Tumor-Initiating Capacity: Depletion of CD44+ Cells and Evidence for Epigenetic Mechanisms

(2011) Hong Yan et al.   PLoS One

Selective killing of K-ras mutant cancer cells by small molecule inducers of oxidative stress

(2011) A. T. Shaw et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

A Cell-Based High-Content Screening Assay Reveals Activators and Inhibitors of Cancer Cell Invasion

(2011) M. Quintavalle et al.   Science Signaling

Cancer-Initiating Enriched Cell Lines from Human Glioblastoma: Preparing for Drug Discovery Assays

(2011) Miriam Romaguera-Ros et al.   Stem Cell Reviews and Reports

Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms

(2010) A. Quintas-Cardama et al.   BLOOD

BAL27862: A Unique Microtubule Destabilizer Active Against Chemorefractory Breast Cancers.

(2010) M. Breuleux et al.   CANCER RESEARCH

A Chromatin-Mediated Reversible Drug-Tolerant State in Cancer Cell Subpopulations

(2010) Sreenath V. Sharma et al.   CELL

Targeting Wnt Signaling: Can We Safely Eradicate Cancer Stem Cells?

(2010) F. Takahashi-Yanaga et al.   CLINICAL CANCER RESEARCH

The long and winding road for the development of tasquinimod as an oral second-generation quinoline-3-carboxamide antiangiogenic drug for the treatment of prostate cancer

(2010) John T Isaacs   EXPERT OPINION ON INVESTIGATIONAL DRUGS

Sorafenib: a clinical and pharmacologic review

(2010) Renuka Iyer et al.   EXPERT OPINION ON PHARMACOTHERAPY

Stochastic acquisition of a stem cell-like state and drug tolerance in leukemia cells stressed by radiation

(2010) Ga-Young Lee et al.   INTERNATIONAL JOURNAL OF HEMATOLOGY

Discovery of 3-[2-(Imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a Potent, Orally Active Pan-Inhibitor of Breakpoint Cluster Region-Abelson (BCR-ABL) Kinase Including the T315I Gatekeeper Mutant

(2010) Wei-Sheng Huang et al.   JOURNAL OF MEDICINAL CHEMISTRY

High-Content Phenotypic Profiling of Drug Response Signatures across Distinct Cancer Cells

(2010) P. D. Caie et al.   MOLECULAR CANCER THERAPEUTICS

ARQ 197, a Novel and Selective Inhibitor of the Human c-Met Receptor Tyrosine Kinase with Antitumor Activity

(2010) N. Munshi et al.   MOLECULAR CANCER THERAPEUTICS

Selective inhibition of BET bromodomains

(2010) Panagis Filippakopoulos et al.   NATURE

Finding the tumor copycat: Therapy fails, patients don't

(2010) Lee M Ellis et al.   NATURE MEDICINE

Cabazitaxel

(2010) Matthew D. Galsky et al.   NATURE REVIEWS DRUG DISCOVERY

Pharmacological reactivation of mutant p53: from protein structure to the cancer patient

(2010) K G Wiman   ONCOGENE

Voreloxin Is an Anticancer Quinolone Derivative that Intercalates DNA and Poisons Topoisomerase II

(2010) Rachael E. Hawtin et al.   PLoS One

The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy

(2010) L. A. Honigberg et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

GDC-0449—A potent inhibitor of the hedgehog pathway

(2009) Kirk D. Robarge et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

A multi-center phase II evaluation of the small molecule survivin suppressor YM155 in patients with unresectable stage III or IV melanoma

(2009) Karl D. Lewis et al.   INVESTIGATIONAL NEW DRUGS

Preclinical characterization of Aurora kinase inhibitor R763/AS703569 identified through an image-based phenotypic screen

(2009) John McLaughlin et al.   JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY

Multicenter Phase II Trial of YM155, a Small-Molecule Suppressor of Survivin, in Patients With Advanced, Refractory, Non–Small-Cell Lung Cancer

(2009) Giuseppe Giaccone et al.   JOURNAL OF CLINICAL ONCOLOGY

Mechanism of action of lenalidomide in hematological malignancies

(2009) Venumadhav Kotla et al.   Journal of Hematology & Oncology

Zalypsis (PM00104) is a potent inducer of  -H2AX foci and reveals the importance of the C ring of trabectedin for transcription-coupled repair inhibition

(2009) J. Guirouilh-Barbat et al.   MOLECULAR CANCER THERAPEUTICS

Small molecule–mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer

(2009) Baozhi Chen et al.   Nature Chemical Biology

Spheroid-based drug screen: considerations and practical approach

(2009) Juergen Friedrich et al.   Nature Protocols

Styryl sulfonyl compounds inhibit translation of cyclin D1 in mantle cell lymphoma cells

(2009) A Prasad et al.   ONCOGENE

Molecular and Phenotypic Characterisation of Paediatric Glioma Cell Lines as Models for Preclinical Drug Development

(2009) Dorine A. Bax et al.   PLoS One

Discovery of Novel Proteasome Inhibitors Using a High-Content Cell-Based Screening System

(2009) Irena Lavelin et al.   PLoS One

Development of a Second-Generation Antiandrogen for Treatment of Advanced Prostate Cancer

(2009) C. Tran et al.   SCIENCE

A small molecule inhibitor of α4 integrin-dependent cell migration

(2008) Jongkook Lee et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Preclinical discovery of ixabepilone, a highly active antineoplastic agent

(2008) Francis Y. F. Lee et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

A History of Cancer Chemotherapy

(2008) Vincent T. DeVita et al.   CANCER RESEARCH

Bendamustine (Treanda) Displays a Distinct Pattern of Cytotoxicity and Unique Mechanistic Features Compared with Other Alkylating Agents

(2008) L. M. Leoni et al.   CLINICAL CANCER RESEARCH

Azacitidine and the beginnings of therapeutic epigenetic modulation

(2008) Kristen O'Dwyer et al.   EXPERT OPINION ON PHARMACOTHERAPY

Phase I Study of ON 01910.Na, a Novel Modulator of the Polo-Like Kinase 1 Pathway, in Adult Patients With Solid Tumors

(2008) Antonio Jimeno et al.   JOURNAL OF CLINICAL ONCOLOGY

Elesclomol induces cancer cell apoptosis through oxidative stress

(2008) J. R. Kirshner et al.   MOLECULAR CANCER THERAPEUTICS

Network pharmacology: the next paradigm in drug discovery

(2008) Andrew L Hopkins   Nature Chemical Biology

BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models

(2008) D Li et al.   ONCOGENE