Drugging “undruggable” genes for cancer treatment: Are we making progress?

APR-246 Combined with Azacitidine (AZA) in TP53 Mutated Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML). a Phase 2 Study By the Groupe Francophone Des Myélodysplasies (GFM)

(2020) Thomas Cluzeau et al.   BLOOD

Phase 2 Results of APR-246 and Azacitidine (AZA) in Patients with TP53 mutant Myelodysplastic Syndromes (MDS) and Oligoblastic Acute Myeloid Leukemia (AML)

(2020) David A Sallman et al.   BLOOD

Blocking Myc to Treat Cancer: Reflecting on Two Decades of Omomyc

(2020) Daniel Massó-Vallés et al.   Cells

Intrinsic cell-penetrating activity propels Omomyc from proof of concept to viable anti-MYC therapy

(2019) Marie-Eve Beaulieu et al.   Science Translational Medicine

The multiple mechanisms that regulate p53 activity and cell fate

(2019) Antonina Hafner et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Progress in targeting RAS with small molecule drugs

(2019) Frank McCormick   BIOCHEMICAL JOURNAL

ALK rearrangements: Biology, detection and opportunities of therapy in non-small cell lung cancer

(2019) Gina Rosas et al.   CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY

c-MYC regulates mRNA translation efficiency and start-site selection in lymphoma

(2019) Kamini Singh et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Direct Ras G12C inhibitors: crossing the rubicon

(2019) Colin R. Lindsay et al.   BRITISH JOURNAL OF CANCER

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

Omomyc reveals new mechanisms to inhibit the MYC oncogene

(2019) Mark J. Demma et al.   MOLECULAR AND CELLULAR BIOLOGY

HER2 and Breast Cancer — A Phenomenal Success Story

(2019) Daniel F. Hayes   NEW ENGLAND JOURNAL OF MEDICINE

Colorectal cancer

(2019) Evelien Dekker et al.   LANCET

Pan-cancer whole-genome analyses of metastatic solid tumours

(2019) Peter Priestley et al.   NATURE

The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity

(2019) Jude Canon et al.   NATURE

Interaction of the oncoprotein transcription factor MYC with its chromatin cofactor WDR5 is essential for tumor maintenance

(2019) Lance R. Thomas et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The KRASG12C Inhibitor MRTX849 Provides Insight toward Therapeutic Susceptibility of KRAS-Mutant Cancers in Mouse Models and Patients

(2019) Jill Hallin et al.   Cancer Discovery

MYC-induced metabolic stress and tumorigenesis

(2018) Adam J. Wolpaw et al.   BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER

The MYC oncogene is a global regulator of the immune response

(2018) Stephanie C. Casey et al.   BLOOD

Targeting KRAS Mutant Cancers with a Covalent G12C-Specific Inhibitor

(2018) Matthew R. Janes et al.   CELL

Precision oncology in the age of integrative genomics

(2018) Chandan Kumar-Sinha et al.   NATURE BIOTECHNOLOGY

The reactivity-driven biochemical mechanism of covalent KRASG12C inhibitors

(2018) Rasmus Hansen et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Novel anti-cancer drug COTI-2 synergizes with therapeutic agents and does not induce resistance or exhibit cross-resistance in human cancer cell lines

(2018) Saman Maleki Vareki et al.   PLoS One

RAS-mediated oncogenic signaling pathways in human malignancies

(2018) Abdul Q. Khan et al.   SEMINARS IN CANCER BIOLOGY

APR-246 reactivates mutant p53 by targeting cysteines 124 and 277

(2018) Qiang Zhang et al.   Cell Death & Disease

The reactivity-driven biochemical mechanism of covalent KRASG12C inhibitors

(2018) Rasmus Hansen et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

(2018) Franz X. Schaub et al.   Cell Systems

Abstract CT033: Safety and early efficacy signals for COTI-2, an orally available small molecule targeting p53, in a phase I trial of recurrent gynecologic cancer

(2018) Shannon N. Westin et al.   CANCER RESEARCH

Farnesyl trasnsferase inhibitors as potential anticancer agents

(2018) Sounak Bagchi et al.   MINI-REVIEWS IN MEDICINAL CHEMISTRY

Tumor penetrating peptides inhibiting MYC as a potent targeted therapeutic strategy for triple-negative breast cancers

(2018) Edina Wang et al.   ONCOGENE

Inhibition of the glutaredoxin and thioredoxin systems and ribonucleotide reductase by mutant p53-targeting compound APR-246

(2018) Lena Haffo et al.   Scientific Reports

The MYC transcription factor network: balancing metabolism, proliferation and oncogenesis

(2018) Patrick A. Carroll et al.   Frontiers of Medicine

MYC Protein Interactome Profiling Reveals Functionally Distinct Regions that Cooperate to Drive Tumorigenesis

(2018) Manpreet Kalkat et al.   MOLECULAR CELL

COSMIC: the Catalogue Of Somatic Mutations In Cancer

(2018) John G Tate et al.   NUCLEIC ACIDS RESEARCH

Pharmacological targeting of RAS: Recent success with direct inhibitors

(2018) John P. O’Bryan   PHARMACOLOGICAL RESEARCH

Mutant p53 as a target for cancer treatment

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

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

Direct inhibition of RAS: Quest for the Holy Grail?

(2017) Russell Spencer-Smith et al.   SEMINARS IN CANCER BIOLOGY

Inhibiting the system xC−/glutathione axis selectively targets cancers with mutant-p53 accumulation

(2017) David S. Liu et al.   Nature Communications

KRAS: The Critical Driver and Therapeutic Target for Pancreatic Cancer

(2017) Andrew M. Waters et al.   Cold Spring Harbor Perspectives in Medicine

Anti-leukaemic effects induced by APR-246 are dependent on induction of oxidative stress and the NFE2L2/HMOX1 axis that can be targeted by PI3K and mTOR inhibitors in acute myeloid leukaemia cells

(2016) Dina Ali et al.   BRITISH JOURNAL OF HAEMATOLOGY

A Small Molecule RAS-Mimetic Disrupts RAS Association with Effector Proteins to Block Signaling

(2016) Sai Krishna Athuluri-Divakar et al.   CELL

Mutant p53: a novel target for the treatment of patients with triple-negative breast cancer?

(2016) N.C. Synnott et al.   INTERNATIONAL JOURNAL OF CANCER

Rigosertib versus best supportive care for patients with high-risk myelodysplastic syndromes after failure of hypomethylating drugs (ONTIME): a randomised, controlled, phase 3 trial

(2016) Guillermo Garcia-Manero et al.   LANCET ONCOLOGY

OmoMYC blunts promoter invasion by oncogenic MYC to inhibit gene expression characteristic of MYC-dependent tumors

(2016) L A Jung et al.   ONCOGENE

Allele-specific inhibitors inactivate mutant KRAS G12C by a trapping mechanism

(2016) P. Lito et al.   SCIENCE

Selective Inhibition of Oncogenic KRAS Output with Small Molecules Targeting the Inactive State

(2016) M. P. Patricelli et al.   Cancer Discovery

COTI-2, a novel small molecule that is active against multiple human cancer cell lines in vitro and in vivo

(2016) Kowthar Y. Salim et al.   Oncotarget

Targeting RAS Membrane Association: Back to the Future for Anti-RAS Drug Discovery?

(2015) A. D. Cox et al.   CLINICAL CANCER RESEARCH

Peptide therapeutics: current status and future directions

(2015) Keld Fosgerau et al.   DRUG DISCOVERY TODAY

Comprehensive genomic profiles of small cell lung cancer

(2015) Julie George et al.   NATURE

APR-246 overcomes resistance to cisplatin and doxorubicin in ovarian cancer cells

(2015) N Mohell et al.   Cell Death & Disease

PRIMA-1Met induces myeloma cell death independent of p53 by impairing the GSH/ROS balance

(2014) B. Tessoulin et al.   BLOOD

TP53 Mutations in Human Cancer: Database Reassessment and Prospects for the Next Decade

(2014) Bernard Leroy et al.   HUMAN MUTATION

Identification of genomic alterations in oesophageal squamous cell cancer

(2014) Yongmei Song et al.   NATURE

An Overview of MYC and Its Interactome

(2014) M. Conacci-Sorrell et al.   Cold Spring Harbor Perspectives in Medicine

Inhibition of Myc family proteins eradicates KRas-driven lung cancer in mice

(2013) L. Soucek et al.   GENES & DEVELOPMENT

K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions

(2013) Jonathan M. Ostrem et al.   NATURE

Modulation of oxidative stress as an anticancer strategy

(2013) Chiara Gorrini et al.   NATURE REVIEWS DRUG DISCOVERY

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

p53 Efficiently Suppresses Tumor Development in the Complete Absence of Its Cell-Cycle Inhibitory and Proapoptotic Effectors p21, Puma, and Noxa

(2013) Liz J. Valente et al.   Cell Reports

A Comprehensive Survey of Ras Mutations in Cancer

(2012) I. A. Prior et al.   CANCER RESEARCH

MYC on the Path to Cancer

(2012) Chi V. Dang   CELL

Comprehensive molecular portraits of human breast tumours

(2012) Daniel C. Koboldt et al.   NATURE

Comprehensive genomic characterization of squamous cell lung cancers

(2012)   NATURE

Integrated genomic analyses of ovarian carcinoma

(2011) D. Bell et al.   NATURE

The Action Mechanism of the Myc Inhibitor Termed Omomyc May Give Clues on How to Target Myc for Cancer Therapy

(2011) Mauro Savino et al.   PLoS One

The landscape of somatic copy-number alteration across human cancers

(2010) Rameen Beroukhim et al.   NATURE

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

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

Structural Biology of the Tumor Suppressor p53

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

Modelling Myc inhibition as a cancer therapy

(2008) Laura Soucek et al.   NATURE