Targeting mutant p53 for cancer therapy: direct and indirect strategies

Eprenetapopt (APR-246) and Azacitidine in TP53-Mutant Myelodysplastic Syndromes

(2021) David A. Sallman et al.   JOURNAL OF CLINICAL ONCOLOGY

Mutant p53 as a Regulator and Target of Autophagy

(2021) Yong Shi et al.   Frontiers in Oncology

Adamantyl Isothiocyanates as Mutant p53 Rescuing Agents and Their Structure–Activity Relationships

(2021) Vladimir Burmistrov et al.   JOURNAL OF MEDICINAL CHEMISTRY

Pharmacokinetic–pharmacodynamic guided optimisation of dose and schedule of CGM097, an HDM2 inhibitor, in preclinical and clinical studies

(2021) Sebastian Bauer et al.   BRITISH JOURNAL OF CANCER

Phase 1 Trial of ALRN-6924, a Dual Inhibitor of MDMX and MDM2, in Patients with Solid Tumors and Lymphomas Bearing Wild-Type TP53

(2021) Mansoor N Saleh et al.   CLINICAL CANCER RESEARCH

Phase I study of daily and weekly regimens of the orally administered MDM2 antagonist idasanutlin in patients with advanced tumors

(2021) Antoine Italiano et al.   INVESTIGATIONAL NEW DRUGS

Phase 1 study of the MDM2 antagonist RO6839921 in patients with acute myeloid leukemia

(2020) Geoffrey L. Uy et al.   INVESTIGATIONAL NEW DRUGS

MiR-509-3 augments the synthetic lethality of PARPi by regulating HR repair in PDX model of HGSOC

(2020) Chenggong Sun et al.   Journal of Hematology & Oncology

Improving cancer immunotherapy using nanomedicines: progress, opportunities and challenges

(2020) John D. Martin et al.   Nature Reviews Clinical Oncology

Phase 1 study of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumours

(2020) David S. Hong et al.   BRITISH JOURNAL OF CANCER

Long noncoding RNA AGPG regulates PFKFB3-mediated tumor glycolytic reprogramming

(2020) Jia Liu et al.   Nature Communications

The Impact of Mutant p53 in the Non-Coding RNA World

(2020) Silvia Di Agostino   Biomolecules

Thirty Years of HDAC Inhibitors: 2020 Insight and Hindsight

(2020) Terence C. S. Ho et al.   JOURNAL OF MEDICINAL CHEMISTRY

Berzosertib plus gemcitabine versus gemcitabine alone in platinum-resistant high-grade serous ovarian cancer: a multicentre, open-label, randomised, phase 2 trial

(2020) Panagiotis A Konstantinopoulos et al.   LANCET ONCOLOGY

MDM2 inhibition: an important step forward in cancer therapy

(2020) Marina Konopleva et al.   LEUKEMIA

Tumorigenic p53 Mutants Undergo Common Structural Disruptions Including Conversion to α‐Sheet Structure

(2020) Dennis Bromley et al.   PROTEIN SCIENCE

Targeting p53 for the treatment of cancer

(2020) Michael J. Duffy et al.   SEMINARS IN CANCER BIOLOGY

Mutant p53 induces Golgi tubulo-vesiculation driving a prometastatic secretome

(2020) Valeria Capaci et al.   Nature Communications

The P53/microRNA network: A potential tumor suppressor with a role in anticancer therapy

(2020) Javad Sargolzaei et al.   PHARMACOLOGICAL RESEARCH

LINC00460-miR-149-5p/miR-150-5p-mutant p53 feedback loop promotes oxaliplatin resistance in colorectal cancer

(2020) Xiangfeng Meng et al.   Molecular Therapy-Nucleic Acids

A Novel cytarabine analog evokes synthetic lethality by targeting MK2 in p53-deficient cancer cells

(2020) Jayoung Song et al.   CANCER LETTERS

Murine double minute 2 inhibition alone or with cytarabine in acute myeloid leukemia: Results from an idasanutlin phase 1/1b study⋆

(2020) Karen Yee et al.   LEUKEMIA RESEARCH

p53-targeted lincRNA-p21 acts as a tumor suppressor by inhibiting JAK2/STAT3 signaling pathways in head and neck squamous cell carcinoma

(2019) Shufang Jin et al.   Molecular Cancer

MiR-223-3p functions as a tumor suppressor in lung squamous cell carcinoma by miR-223-3p-mutant p53 regulatory feedback loop

(2019) Peng Luo et al.   JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH

A single-center, open-label study investigating the excretion balance, pharmacokinetics, metabolism, and absolute bioavailability of a single oral dose of [14C]-labeled idasanutlin and an intravenous tracer dose of [13C]-labeled idasanutlin in a single cohort of patients with solid tumors

(2019) Zsuzsanna Pápai et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

MDM2 antagonists as a novel treatment option for acute myeloid leukemia: perspectives on the therapeutic potential of idasanutlin (RG7388)

(2019) Arushi Khurana et al.   OncoTargets and Therapy

Mutant p53 and Cellular Stress Pathways: A Criminal Alliance That Promotes Cancer Progression

(2019) Gabriella D’Orazi et al.   Cancers

A decade of clinical development of PARP inhibitors in perspective

(2019) J Mateo et al.   ANNALS OF ONCOLOGY

COTI-2 reactivates mutant p53 and inhibits growth of triple-negative breast cancer cells

(2019) Naoise C. Synnott et al.   BREAST CANCER RESEARCH AND TREATMENT

The CHK1 Inhibitor Prexasertib Exhibits Monotherapy Activity in High-Grade Serous Ovarian Cancer Models and Sensitizes to PARP Inhibition

(2019) Kalindi Parmar et al.   CLINICAL CANCER RESEARCH

The past, present and future of potential small-molecule drugs targeting p53-MDM2/MDMX for cancer therapy

(2019) Yao Liu et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

P53-R273H mutation enhances colorectal cancer stemness through regulating specific lncRNAs

(2019) Yuechao Zhao et al.   JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH

The biogenesis, biology and characterization of circular RNAs

(2019) Lasse S. Kristensen et al.   NATURE REVIEWS GENETICS

Clinical relevance of TP53 hotspot mutations in high-grade serous ovarian cancers

(2019) Musaffe Tuna et al.   BRITISH JOURNAL OF CANCER

The Role of Non-coding RNAs in Oncology

(2019) Frank J. Slack et al.   CELL

A structure-guided molecular chaperone approach for restoring the transcriptional activity of the p53 cancer mutant Y220C

(2019) Matthias R Bauer et al.   Future Medicinal Chemistry

A phase 1 study of the MDM2 antagonist RO6839921, a pegylated prodrug of idasanutlin, in patients with advanced solid tumors

(2019) Albiruni R. Abdul Razak et al.   INVESTIGATIONAL NEW DRUGS

MDM2 inhibitor APG-115 synergizes with PD-1 blockade through enhancing antitumor immunity in the tumor microenvironment

(2019) Douglas D. Fang et al.   Journal for ImmunoTherapy of Cancer

Glucocorticoid induces human beta cell dysfunction by involving riborepressor GAS5 LincRNA

(2019) Jonathan L.S. Esguerra et al.   Molecular Metabolism

Targeting autophagy in cancer

(2018) Angelique V. Onorati et al.   CANCER

Functional Classification and Experimental Dissection of Long Noncoding RNAs

(2018) Florian Kopp et al.   CELL

Enhanced breast cancer progression by mutant p53 is inhibited by the circular RNA circ-Ccnb1

(2018) Ling Fang et al.   CELL DEATH AND DIFFERENTIATION

A Phase I Clinical Trial of AZD1775 in Combination with Neoadjuvant Weekly Docetaxel and Cisplatin before Definitive Therapy in Head and Neck Squamous Cell Carcinoma

(2018) Eduardo Méndez et al.   CLINICAL CANCER RESEARCH

Phase I Study of ATR Inhibitor M6620 in Combination With Topotecan in Patients With Advanced Solid Tumors

(2018) Anish Thomas et al.   JOURNAL OF CLINICAL ONCOLOGY

A Systematic p53 Mutation Library Links Differential Functional Impact to Cancer Mutation Pattern and Evolutionary Conservation

(2018) Eran Kotler et al.   MOLECULAR CELL

ATR/CHK1 inhibitors and cancer therapy

(2018) Zhaojun Qiu et al.   RADIOTHERAPY AND ONCOLOGY

Dual inhibition of MDMX and MDM2 as a therapeutic strategy in leukemia

(2018) Luis A. Carvajal et al.   Science Translational Medicine

MiR-142-3p is downregulated in aggressive p53 mutant mouse models of pancreatic ductal adenocarcinoma by hypermethylation of its locus

(2018) Jack D. Godfrey et al.   Cell Death & Disease

Mutant p53 cancers reprogram macrophages to tumor supporting macrophages via exosomal miR-1246

(2018) Tomer Cooks et al.   Nature Communications

Long Non-coding MIR205HG Depletes Hsa-miR-590-3p Leading to Unrestrained Proliferation in Head and Neck Squamous Cell Carcinoma

(2018) Silvia Di Agostino et al.   Theranostics

Gain-of-Function (GOF) Mutant p53 as Actionable Therapeutic Target

(2018) Ramona Schulz-Heddergott et al.   Cancers

Dose and schedule determine distinct molecular mechanisms underlying the efficacy of the p53-MDM2 inhibitor HDM201

(2018) Sébastien Jeay et al.   CANCER RESEARCH

Effect of Mutant p53 Proteins on Glycolysis and Mitochondrial Metabolism

(2017) Matilda Eriksson et al.   MOLECULAR AND CELLULAR BIOLOGY

Regulation of G2/M Transition by Inhibition of WEE1 and PKMYT1 Kinases

(2017) et al.   MOLECULES

Therapeutic targeting of p53: all mutants are equal, but some mutants are more equal than others

(2017) Kanaga Sabapathy et al.   Nature Reviews Clinical Oncology

Synthetic lethality and cancer

(2017) Nigel J. O'Neil et al.   NATURE REVIEWS GENETICS

A mitosis-specific and R loop–driven ATR pathway promotes faithful chromosome segregation

(2017) Lilian Kabeche et al.   SCIENCE

The p53 Pathway: Origins, Inactivation in Cancer, and Emerging Therapeutic Approaches

(2016) Andreas C. Joerger et al.   Annual Review of Biochemistry

The Roles of MDM2 and MDMX in Cancer

(2016) Orit Karni-Schmidt et al.   Annual Review of Pathology-Mechanisms of Disease

A Designed Inhibitor of p53 Aggregation Rescues p53 Tumor Suppression in Ovarian Carcinomas

(2016) Alice Soragni et al.   CANCER CELL

Inhibition of glycolytic enzyme hexokinase II (HK2) suppresses lung tumor growth

(2016) Huanan Wang et al.   Cancer Cell International

XistandTsixTranscription Dynamics Is Regulated by the X-to-Autosome Ratio and Semistable Transcriptional States

(2016) Friedemann Loos et al.   MOLECULAR AND CELLULAR BIOLOGY

Expression of ANRIL-Polycomb Complexes-CDKN2A/B/ARF Genes in Breast Tumors: Identification of a Two-Gene (EZH2/CBX7) Signature with Independent Prognostic Value

(2016) D. Meseure et al.   MOLECULAR CANCER RESEARCH

Mutant p53 proteins counteract autophagic mechanism sensitizing cancer cells to mTOR inhibition

(2016) Marco Cordani et al.   Molecular Oncology

Non-coding RNAs as drug targets

(2016) Masayuki Matsui et al.   NATURE REVIEWS DRUG DISCOVERY

Unique features of long non-coding RNA biogenesis and function

(2016) Jeffrey J. Quinn et al.   NATURE REVIEWS GENETICS

Non-coding RNAs in Development and Disease: Background, Mechanisms, and Therapeutic Approaches

(2016) Julia Beermann et al.   PHYSIOLOGICAL REVIEWS

2-Sulfonylpyrimidines: Mild alkylating agents with anticancer activity toward p53-compromised cells

(2016) Matthias R. Bauer et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Differential regulated microRNA by wild type and mutant p53 in induced pluripotent stem cells

(2016) Francesca Grespi et al.   Cell Death & Disease

LncRNA GClnc1 Promotes Gastric Carcinogenesis and May Act as a Modular Scaffold of WDR5 and KAT2A Complexes to Specify the Histone Modification Pattern

(2016) T.-T. Sun et al.   Cancer Discovery

The Cell-Cycle Arrest and Apoptotic Functions of p53 in Tumor Initiation and Progression

(2016) Jiandong Chen   Cold Spring Harbor Perspectives in Medicine

The Role of MDM2 Amplification and Overexpression in Tumorigenesis

(2016) Jonathan D. Oliner et al.   Cold Spring Harbor Perspectives in Medicine

Long noncoding RNAs in the p53 network

(2016) Ritu Chaudhary et al.   Wiley Interdisciplinary Reviews-RNA

Clinical pharmacology characterization of RG7112, an MDM2 antagonist, in patients with advanced solid tumors

(2015) Amita Patnaik et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

Small-Molecule NSC59984 Restores p53 Pathway Signaling and Antitumor Effects against Colorectal Cancer via p73 Activation and Degradation of Mutant p53

(2015) Shengliang Zhang et al.   CANCER RESEARCH

Small-Molecule Reactivation of Mutant p53 to Wild-Type-like p53 through the p53-Hsp40 Regulatory Axis

(2015) Masatsugu Hiraki et al.   CHEMISTRY & BIOLOGY

Results of the Phase I Trial of RG7112, a Small-Molecule MDM2 Antagonist in Leukemia

(2015) M. Andreeff et al.   CLINICAL CANCER RESEARCH

p53-dependent non-coding RNA networks in chronic lymphocytic leukemia

(2015) C J Blume et al.   LEUKEMIA

p53 in survival, death and metabolic health: a lifeguard with a licence to kill

(2015) Flore Kruiswijk et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Targeting Oncogenic Mutant p53 for Cancer Therapy

(2015) Alejandro Parrales et al.   Frontiers in Oncology

Targeting of miR34a-NOTCH1 Axis Reduced Breast Cancer Stemness and Chemoresistance

(2014) E. Y. Park et al.   CANCER RESEARCH

Mutant p53 Drives Pancreatic Cancer Metastasis through Cell-Autonomous PDGF Receptor β Signaling

(2014) Susann Weissmueller et al.   CELL

The ENCODE Project and Perspectives on Pathways

(2014) Vinicius Tragante et al.   GENETIC EPIDEMIOLOGY

New and emerging HDAC inhibitors for cancer treatment

(2014) Alison C. West et al.   JOURNAL OF CLINICAL INVESTIGATION

Development of Synthetic Lethality Anticancer Therapeutics

(2014) Bingliang Fang   JOURNAL OF MEDICINAL CHEMISTRY

Polo-like kinases: structural variations lead to multiple functions

(2014) Sihem Zitouni et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Applying Synthetic Lethality for the Selective Targeting of Cancer

(2014) Donal P. McLornan et al.   NEW ENGLAND JOURNAL OF MEDICINE

An update on LNCipedia: a database for annotated human lncRNA sequences

(2014) Pieter-Jan Volders et al.   NUCLEIC ACIDS RESEARCH

A mutant p53/let-7i-axis-regulated gene network drives cell migration, invasion and metastasis

(2014) M Subramanian et al.   ONCOGENE

Pla2g16 phospholipase mediates gain-of-function activities of mutant p53

(2014) S. Xiong et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Hexokinase 2-Mediated Warburg Effect Is Required for PTEN- and p53-Deficiency-Driven Prostate Cancer Growth

(2014) Lei Wang et al.   Cell Reports

Degradation of NF-κB, p53 and other regulatory redox-sensitive proteins by thiol-conjugating and -nitrosylating drugs in human tumor cells

(2013) Ameya Paranjpe et al.   CARCINOGENESIS

Depletion of a Putatively Druggable Class of Phosphatidylinositol Kinases Inhibits Growth of p53-Null Tumors

(2013) Brooke M. Emerling et al.   CELL

Chaperone-mediated autophagy degrades mutant p53

(2013) H. Vakifahmetoglu-Norberg et al.   GENES & DEVELOPMENT

RCP-driven α5β1 recycling suppresses Rac and promotes RhoA activity via the RacGAP1–IQGAP1 complex

(2013) Guillaume Jacquemet et al.   JOURNAL OF CELL BIOLOGY

Progress in microRNA delivery

(2013) Yu Zhang et al.   JOURNAL OF CONTROLLED RELEASE

Activation of p53 with Nutlin-3a radiosensitizes lung cancer cells via enhancing radiation-induced premature senescence

(2013) Hongmei Luo et al.   LUNG CANCER

Gain-of-function mutant p53 downregulates miR-223 contributing to chemoresistance of cultured tumor cells

(2013) S Masciarelli et al.   ONCOGENE

APR-246/PRIMA-1MET inhibits thioredoxin reductase 1 and converts the enzyme to a dedicated NADPH oxidase

(2013) X Peng et al.   Cell Death & Disease

The p53 miRNA interactome and its potential role in the cancer clinic

(2013) Jonathan Krell et al.   Epigenomics

Computational identification of a transiently open L1/S3 pocket for reactivation of mutant p53

(2013) Christopher D. Wassman et al.   Nature Communications

Tumour-associated mutant p53 drives the Warburg effect

(2013) Cen Zhang et al.   Nature Communications

miRNA-34 Prevents Cancer Initiation and Progression in a Therapeutically Resistant K-ras and p53-Induced Mouse Model of Lung Adenocarcinoma

(2012) A. L. Kasinski et al.   CANCER RESEARCH

p53 expression controls prostate cancer sensitivity to chemotherapy and the MDM2 inhibitor Nutlin-3

(2012) William H. Chappell et al.   CELL CYCLE

GENCODE: The reference human genome annotation for The ENCODE Project

(2012) J. Harrow et al.   GENOME RESEARCH

Induction of mitotic cell death by overriding G2/M checkpoint in endometrial cancer cells with non-functional p53

(2012) Xiangbing Meng et al.   GYNECOLOGIC ONCOLOGY

Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-of-mechanism study

(2012) Isabelle Ray-Coquard et al.   LANCET ONCOLOGY

The Plk1 inhibitor BI 2536 in patients with refractory or relapsed non-Hodgkin lymphoma: a phase I, open-label, single dose-escalation study

(2012) Julie M. Vose et al.   LEUKEMIA & LYMPHOMA

Histone deacetylase inhibitors suppress mutant p53 transcription via histone deacetylase 8

(2012) W Yan et al.   ONCOGENE

Forced activation of Cdk1 via wee1 inhibition impairs homologous recombination

(2012) M Krajewska et al.   ONCOGENE

Mutant p53 gain-of-function induces epithelial–mesenchymal transition through modulation of the miR-130b–ZEB1 axis

(2012) P Dong et al.   ONCOGENE

Activation of the p53 pathway by small-molecule-induced MDM2 and MDMX dimerization

(2012) B. Graves et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Secreted microRNAs: a new form of intercellular communication

(2012) Xi Chen et al.   TRENDS IN CELL BIOLOGY

Hallmarks of Cancer: The Next Generation

(2011) Douglas Hanahan et al.   CELL

SAHA shows preferential cytotoxicity in mutant p53 cancer cells by destabilizing mutant p53 through inhibition of the HDAC6-Hsp90 chaperone axis

(2011) D Li et al.   CELL DEATH AND DIFFERENTIATION

MK-1775, a Novel Wee1 Kinase Inhibitor, Radiosensitizes p53-Defective Human Tumor Cells

(2011) K. A. Bridges et al.   CLINICAL CANCER RESEARCH

Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR

(2011) Philip M Reaper et al.   Nature Chemical Biology

Synthesis of cytochrome c oxidase 2: a p53-dependent metabolic regulator that promotes respiratory function and protects glioma and colon cancer cells from hypoxia-induced cell death

(2011) C Wanka et al.   ONCOGENE

Blockade of Hsp90 by 17AAG antagonizes MDMX and synergizes with Nutlin to induce p53-mediated apoptosis in solid tumors

(2011) A V Vaseva et al.   Cell Death & Disease

Regulation of mRNA Translation and Stability by microRNAs

(2010) Marc Robert Fabian et al.   Annual Review of Biochemistry

Targeting Cancer Cell Metabolism: The Combination of Metformin and 2-Deoxyglucose Induces p53-Dependent Apoptosis in Prostate Cancer Cells

(2010) I. Ben Sahra et al.   CANCER RESEARCH

SCH529074, a Small Molecule Activator of Mutant p53, Which Binds p53 DNA Binding Domain (DBD), Restores Growth-suppressive Function to Mutant p53 and Interrupts HDM2-mediated Ubiquitination of Wild Type p53

(2010) Mark Demma et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Gain of oncogenic function of p53 mutants regulates E-cadherin expression uncoupled from cell invasion in colon cancer cells

(2010) L. Roger et al.   JOURNAL OF CELL SCIENCE

Gambogic acid-induced degradation of mutant p53 is mediated by proteasome and related to CHIP

(2010) Jia Wang et al.   JOURNAL OF CELLULAR BIOCHEMISTRY

miR-200 Inhibits Lung Adenocarcinoma Cell Invasion and Metastasis by Targeting Flt1/VEGFR1

(2010) J. D. Roybal et al.   MOLECULAR CANCER RESEARCH

Nutlin-3a Induces Cytoskeletal Rearrangement and Inhibits the Migration and Invasion Capacity of p53 Wild-Type Cancer Cells

(2010) Diarmuid M. Moran et al.   MOLECULAR CANCER THERAPEUTICS

TP53 Mutations in Human Cancers: Origins, Consequences, and Clinical Use

(2009) M. Olivier et al.   Cold Spring Harbor Perspectives in Biology

Small-Molecule Inhibitors of the MDM2-p53 Protein-Protein Interaction to Reactivate p53 Function: A Novel Approach for Cancer Therapy

(2008) Sanjeev Shangary et al.   Annual Review of Pharmacology and Toxicology

A novel p53 rescue compound induces p53-dependent growth arrest and sensitises glioma cells to Apo2L/TRAIL-induced apoptosis

(2008) L Weinmann et al.   CELL DEATH AND DIFFERENTIATION

The inherent instability of mutant p53 is alleviated by Mdm2 or p16INK4a loss

(2008) T. Terzian et al.   GENES & DEVELOPMENT

Mutant p53 targeting by the low molecular weight compound STIMA-1

(2008) Nicole Zache et al.   Molecular Oncology

p53 regulates glucose metabolism through an IKK-NF-κB pathway and inhibits cell transformation

(2008) Keiko Kawauchi et al.   NATURE CELL BIOLOGY

ATR: an essential regulator of genome integrity

(2008) Karlene A. Cimprich et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Small-molecule RETRA suppresses mutant p53-bearing cancer cells through a p73-dependent salvage pathway

(2008) J. E. Kravchenko et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Targeted rescue of a destabilized mutant of p53 by an in silico screened drug

(2008) F. M. Boeckler et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA