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

New therapeutic strategies to treat human cancers expressing mutant p53 proteins

(2018) Giovanni Blandino et al.   JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH

Restoring the p53 ‘Guardian’ Phenotype in p53-Deficient Tumor Cells with CRISPR/Cas9

(2018) Sergiu Chira et al.   TRENDS IN BIOTECHNOLOGY

Monoclonal Antibodies against Specific p53 Hotspot Mutants as Potential Tools for Precision Medicine

(2018) Le-Ann Hwang et al.   Cell Reports

Mutant p53 as a target for cancer treatment

(2017) Michael J. Duffy et al.   EUROPEAN JOURNAL OF CANCER

Lung tumors with distinct p53 mutations respond similarly to p53 targeted therapy but exhibit genotype-specific statin sensitivity

(2017) Frances K. Turrell et al.   GENES & DEVELOPMENT

Targeting Heat Shock Proteins in Cancer: A Promising Therapeutic Approach

(2017) et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Mutant p53 establishes targetable tumor dependency by promoting unscheduled replication

(2017) Shilpa Singh et al.   JOURNAL OF CLINICAL INVESTIGATION

Mutant p53 in Cancer: Accumulation, Gain-of-Function, and Therapy

(2017) Xuetian Yue et al.   JOURNAL OF MOLECULAR BIOLOGY

Mechanical cues control mutant p53 stability through a mevalonate–RhoA axis

(2017) Eleonora Ingallina et al.   NATURE CELL BIOLOGY

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

Regulation of heat shock transcription factors and their roles in physiology and disease

(2017) Rocio Gomez-Pastor et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Reviving the guardian of the genome: Small molecule activators of p53

(2017) Daniel Nguyen et al.   PHARMACOLOGY & THERAPEUTICS

p53 loss-of-heterozygosity is a necessary prerequisite for mutant p53 stabilization and gain-of-function in vivo

(2017) Evguenia M Alexandrova et al.   Cell Death & Disease

Exploiting the p53 Pathway for Therapy

(2017) Chit Fang Cheok et al.   Cold Spring Harbor Perspectives in Medicine

PRIMA-1 and PRIMA-1Met (APR-246): From Mutant/Wild Type p53 Reactivation to Unexpected Mechanisms Underlying Their Potent Anti-Tumor Effect in Combinatorial Therapies

(2017) Anne Perdrix et al.   Cancers

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

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

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

(2016) Alice Soragni et al.   CANCER CELL

Reactivation of mutant p53 by a dietary-related compound phenethyl isothiocyanate inhibits tumor growth

(2016) M Aggarwal et al.   CELL DEATH AND DIFFERENTIATION

Depleting stabilized GOF mutant p53 proteins by inhibiting molecular folding chaperones: a new promise in cancer therapy

(2016) Evguenia M Alexandrova et al.   CELL DEATH AND DIFFERENTIATION

Targeting mutant p53 in cancer: a long road to precision therapy

(2016) Fiamma Mantovani et al.   FEBS Journal

Proteasome machinery is instrumental in a common gain-of-function program of the p53 missense mutants in cancer

(2016) Dawid Walerych et al.   NATURE CELL BIOLOGY

DNAJA1 controls the fate of misfolded mutant p53 through the mevalonate pathway

(2016) Alejandro Parrales et al.   NATURE CELL BIOLOGY

Heat Shock Proteins Promote Cancer: It's a Protection Racket

(2016) Stuart K. Calderwood et al.   TRENDS IN BIOCHEMICAL SCIENCES

Cancer therapeutic approach based on conformational stabilization of mutant p53 protein by small peptides

(2016) Perry Tal et al.   Oncotarget

Oncogenic Mutant p53 Gain of Function Nourishes the Vicious Cycle of Tumor Development and Cancer Stem-Cell Formation

(2016) Yoav Shetzer et al.   Cold Spring Harbor Perspectives in Medicine

Transcriptional Regulation by Wild-Type and Cancer-Related Mutant Forms of p53

(2016) Neil T. Pfister et al.   Cold Spring Harbor Perspectives in Medicine

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

(2015) Masatsugu Hiraki et al.   CHEMISTRY & BIOLOGY

Reactivating mutant p53 using small molecules as zinc metallochaperones: awakening a sleeping giant in cancer

(2015) Adam R. Blanden et al.   DRUG DISCOVERY TODAY

Peptide therapeutics: current status and future directions

(2015) Keld Fosgerau et al.   DRUG DISCOVERY TODAY

Improving survival by exploiting tumour dependence on stabilized mutant p53 for treatment

(2015) E. M. Alexandrova et al.   NATURE

Gain-of-function p53 mutants co-opt chromatin pathways to drive cancer growth

(2015) Jiajun Zhu et al.   NATURE

Statins are potential anticancerous agents (Review)

(2015) ABDULLAH K. ALTWAIRGI   ONCOLOGY REPORTS

Mutant p53: One, No One, and One Hundred Thousand

(2015) Dawid Walerych et al.   Frontiers in Oncology

Small molecule restoration of wildtype structure and function of mutant p53 using a novel zinc-metallochaperone based mechanism

(2015) Xin Yu et al.   Oncotarget

Mutant p53 in Cancer: New Functions and Therapeutic Opportunities

(2014) Patricia A.J. Muller et al.   CANCER CELL

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

(2014) Susann Weissmueller et al.   CELL

Phenethyl isothiocyanate induces DNA damage-associated G2/M arrest and subsequent apoptosis in oral cancer cells with varying p53 mutations

(2014) Yao-Tsung Yeh et al.   FREE RADICAL BIOLOGY AND MEDICINE

A gain-of-function mutant p53–HSF1 feed forward circuit governs adaptation of cancer cells to proteotoxic stress

(2014) D Li et al.   Cell Death & Disease

HER2/ErbB2 activates HSF1 and thereby controls HSP90 clients including MIF in HER2-overexpressing breast cancer

(2014) R Schulz et al.   Cell Death & Disease

Unequal prognostic potentials of p53 gain-of-function mutations in human cancers associate with drug-metabolizing activity

(2014) J Xu et al.   Cell Death & Disease

Prodigiosin Rescues Deficient p53 Signaling and Antitumor Effects via Upregulating p73 and Disrupting Its Interaction with Mutant p53

(2013) B. Hong et al.   CANCER RESEARCH

Two hot spot mutant p53 mouse models display differential gain of function in tumorigenesis

(2013) W Hanel et al.   CELL DEATH AND DIFFERENTIATION

PRIMA-1Met/APR-246 Displays High Antitumor Activity in Multiple Myeloma By Induction of p73 and Noxa

(2013) Manujendra N. Saha et al.   MOLECULAR CANCER THERAPEUTICS

Small molecule induced reactivation of mutant p53 in cancer cells

(2013) Xiangrui Liu et al.   NUCLEIC ACIDS RESEARCH

Spliced MDM2 isoforms promote mutant p53 accumulation and gain-of-function in tumorigenesis

(2013) Tongsen Zheng et al.   Nature Communications

Cell-type, Dose, and Mutation-type Specificity Dictate Mutant p53 Functions In Vivo

(2012) Ming Kei Lee et al.   CANCER CELL

Allele-Specific p53 Mutant Reactivation

(2012) Xin Yu et al.   CANCER CELL

Mutant p53 Disrupts Mammary Tissue Architecture via the Mevalonate Pathway

(2012) William A. Freed-Pastor et al.   CELL

Hsp90 Molecular Chaperone Inhibitors: Are We There Yet?

(2012) L. Neckers et al.   CLINICAL CANCER RESEARCH

Mutant p53: one name, many proteins

(2012) W. A. Freed-Pastor et al.   GENES & DEVELOPMENT

Loss of tumor suppressor NF1 activates HSF1 to promote carcinogenesis

(2012) Chengkai Dai et al.   JOURNAL OF CLINICAL INVESTIGATION

Inhibiting the HSP90 chaperone destabilizes macrophage migration inhibitory factor and thereby inhibits breast tumor progression

(2012) Ramona Schulz et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Regulation of HSF1 Function in the Heat Stress Response: Implications in Aging and Disease

(2011) Julius Anckar et al.   Annual Review of Biochemistry

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

Molecular chaperones in mammary cancer growth and breast tumor therapy

(2011) Stuart K. Calderwood et al.   JOURNAL OF CELLULAR BIOCHEMISTRY

Restoring expression of wild-type p53 suppresses tumor growth but does not cause tumor regression in mice with a p53 missense mutation

(2011) Yongxing Wang et al.   JOURNAL OF CLINICAL INVESTIGATION

Dominant-Negative Features of Mutant TP53 in Germline Carriers Have Limited Impact on Cancer Outcomes

(2011) P. Monti et al.   MOLECULAR CANCER RESEARCH

Functional Inactivation of Endogenous MDM2 and CHIP by HSP90 Causes Aberrant Stabilization of Mutant p53 in Human Cancer Cells

(2011) D. Li et al.   MOLECULAR CANCER RESEARCH

High levels of nuclear heat-shock factor 1 (HSF1) are associated with poor prognosis in breast cancer

(2011) S. Santagata et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Inducible Hsp70 in the Regulation of Cancer Cell Survival: Analysis of Chaperone Induction, Expression and Activity

(2011) Elisa Zorzi et al.   Cancers

HSP90 at the hub of protein homeostasis: emerging mechanistic insights

(2010) Mikko Taipale et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

PRIMA-1 Reactivates Mutant p53 by Covalent Binding to the Core Domain

(2009) Jeremy M.R. Lambert et al.   CANCER CELL

Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis

(2009) J M R Lambert et al.   ONCOGENE

Structural Biology of the Tumor Suppressor p53

(2008) Andreas C. Joerger et al.   Annual Review of Biochemistry

Statins Increase p21 through Inhibition of Histone Deacetylase Activity and Release of Promoter-Associated HDAC1/2

(2008) Y.-C. Lin et al.   CANCER RESEARCH

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

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

Chaperone-dependent stabilization and degradation of p53 mutants

(2008) P Muller et al.   ONCOGENE

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