Synthetic lethal therapies for cancer: what’s next after PARP inhibitors?

IDH1/2Mutations Sensitize Acute Myeloid Leukemia to PARP Inhibition and This Is Reversed by IDH1/2-Mutant Inhibitors

(2018) Remco J. Molenaar et al.   CLINICAL CANCER RESEARCH

Alcohol and endogenous aldehydes damage chromosomes and mutate stem cells

(2018) Juan I. Garaycoechea et al.   NATURE

Succinate dehydrogenase (SDH)-deficient neoplasia

(2017) Anthony J Gill   HISTOPATHOLOGY

The genetic landscape of endometrial clear cell carcinomas

(2017) Deborah F DeLair et al.   JOURNAL OF PATHOLOGY

Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial

(2017) Elizabeth M Swisher et al.   LANCET ONCOLOGY

Modeling Therapy Resistance in BRCA1/2 -Mutant Cancers

(2017) Amy Dréan et al.   MOLECULAR CANCER THERAPEUTICS

Genomic deletion of malic enzyme 2 confers collateral lethality in pancreatic cancer

(2017) Prasenjit Dey et al.   NATURE

Synthetic essentiality of chromatin remodelling factor CHD1 in PTEN-deficient cancer

(2017) Di Zhao et al.   NATURE

ARID1A-mutated ovarian cancers depend on HDAC6 activity

(2017) Benjamin G. Bitler et al.   NATURE CELL BIOLOGY

Computational correction of copy number effect improves specificity of CRISPR–Cas9 essentiality screens in cancer cells

(2017) Robin M Meyers et al.   NATURE GENETICS

Marked for death: targeting epigenetic changes in cancer

(2017) Sophia Xiao Pfister et al.   NATURE REVIEWS DRUG DISCOVERY

Emerging and evolving concepts in gene essentiality

(2017) Giulia Rancati et al.   NATURE REVIEWS GENETICS

Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation

(2017) Mark Robson et al.   NEW ENGLAND JOURNAL OF MEDICINE

PRC2-mediated repression of SMARCA2 predicts EZH2 inhibitor activity in SWI/SNF mutant tumors

(2017) Thomas Januario et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

PARP inhibitors: Synthetic lethality in the clinic

(2017) Christopher J. Lord et al.   SCIENCE

HIF activation causes synthetic lethality between the VHL tumor suppressor and the EZH1 histone methyltransferase

(2017) Abhishek A. Chakraborty et al.   Science Translational Medicine

2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity

(2017) Parker L. Sulkowski et al.   Science Translational Medicine

Induction of synthetic lethality in IDH1-mutated gliomas through inhibition of Bcl-xL

(2017) Georg Karpel-Massler et al.   Nature Communications

Identifying and Targeting Sporadic Oncogenic Genetic Aberrations in Mouse Models of Triple-Negative Breast Cancer

(2017) Hui Liu et al.   Cancer Discovery

Synthetic Lethal Vulnerabilities in KRAS -Mutant Cancers

(2017) Andrew J. Aguirre et al.   Cold Spring Harbor Perspectives in Medicine

A Compendium of Co-regulated Protein Complexes in Breast Cancer Reveals Collateral Loss Events

(2017) Colm J. Ryan et al.   Cell Systems

Targeting MYC in cancer therapy: RNA processing offers new opportunities

(2016) Cheryl M. Koh et al.   BIOESSAYS

Perturb-Seq: Dissecting Molecular Circuits with Scalable Single-Cell RNA Profiling of Pooled Genetic Screens

(2016) Atray Dixit et al.   CELL

PARP Inhibitor Activity Correlates with SLFN11 Expression and Demonstrates Synergy with Temozolomide in Small Cell Lung Cancer

(2016) Benjamin H. Lok et al.   CLINICAL CANCER RESEARCH

PARP inhibitor combination therapy

(2016) Amy Dréan et al.   CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY

Comprehensive mutation profiling of mucinous gastric carcinoma

(2016) Hirofumi Rokutan et al.   JOURNAL OF PATHOLOGY

Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial

(2016) Jonathan A Ledermann et al.   LANCET ONCOLOGY

Synthetic Lethal Targeting of ARID1A -Mutant Ovarian Clear Cell Tumors with Dasatinib

(2016) Rowan E. Miller et al.   MOLECULAR CANCER THERAPEUTICS

Inhibition of fatty acid oxidation as a therapy for MYC-overexpressing triple-negative breast cancer

(2016) Roman Camarda et al.   NATURE MEDICINE

PIM1 kinase inhibition as a targeted therapy against triple-negative breast tumors with elevated MYC expression

(2016) Dai Horiuchi et al.   NATURE MEDICINE

Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer

(2016) Mansoor R. Mirza et al.   NEW ENGLAND JOURNAL OF MEDICINE

Rho-associated kinase 1 inhibition is synthetically lethal with von Hippel-Lindau deficiency in clear cell renal cell carcinoma

(2016) J M Thompson et al.   ONCOGENE

Disordered methionine metabolism in MTAP/CDKN2A-deleted cancers leads to dependence on PRMT5

(2016) Konstantinos J. Mavrakis et al.   SCIENCE

MTAPdeletion confers enhanced dependency on the PRMT5 arginine methyltransferase in cancer cells

(2016) Gregory V. Kryukov et al.   SCIENCE

Targeting DNA Repair in Cancer: Beyond PARP Inhibitors

(2016) Jessica S. Brown et al.   Cancer Discovery

Large-Scale Profiling of Kinase Dependencies in Cancer Cell Lines

(2016) James Campbell et al.   Cell Reports

MTAP Deletions in Cancer Create Vulnerability to Targeting of the MAT2A/PRMT5/RIOK1 Axis

(2016) Katya Marjon et al.   Cell Reports

Sustained E2F-Dependent Transcription Is a Key Mechanism to Prevent Replication-Stress-Induced DNA Damage

(2016) Cosetta Bertoli et al.   Cell Reports

Inhibiting WEE1 Selectively Kills Histone H3K36me3-Deficient Cancers by dNTP Starvation

(2015) Sophia X. Pfister et al.   CANCER CELL

A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer

(2015) Felix Dietlein et al.   CELL

Integrative Clinical Genomics of Advanced Prostate Cancer

(2015) Dan Robinson et al.   CELL

RAS Synthetic Lethal Screens Revisited: Still Seeking the Elusive Prize?

(2015) J. Downward   CLINICAL CANCER RESEARCH

Synthetic lethality in chronic lymphocytic leukaemia with DNA damage response defects by targeting the ATR pathway

(2015) Marwan Kwok et al.   LANCET

Homologous-recombination-deficient tumours are dependent on Polθ-mediated repair

(2015) Raphael Ceccaldi et al.   NATURE

Mammalian polymerase θ promotes alternative NHEJ and suppresses recombination

(2015) Pedro A. Mateos-Gomez et al.   NATURE

Whole genomes redefine the mutational landscape of pancreatic cancer

(2015) Nicola Waddell et al.   NATURE

Pyruvate carboxylation enables growth of SDH-deficient cells by supporting aspartate biosynthesis

(2015) Simone Cardaci et al.   NATURE CELL BIOLOGY

Isocitrate dehydrogenase 1 and 2 mutations induce BCL-2 dependence in acute myeloid leukemia

(2015) Steven M Chan et al.   NATURE MEDICINE

SWI/SNF-mutant cancers depend on catalytic and non-catalytic activity of EZH2

(2015) Kimberly H Kim et al.   NATURE MEDICINE

Synthetic lethality by targeting EZH2 methyltransferase activity in ARID1A-mutated cancers

(2015) Benjamin G Bitler et al.   NATURE MEDICINE

Targeting Notch, Hedgehog and Wnt pathways in cancer stem cells: clinical update

(2015) Naoko Takebe et al.   Nature Reviews Clinical Oncology

Hitting cancers’ weak spots: vulnerabilities imposed by p53 mutation

(2015) Evrim Gurpinar et al.   TRENDS IN CELL BIOLOGY

ARID1A Deficiency Impairs the DNA Damage Checkpoint and Sensitizes Cells to PARP Inhibitors

(2015) J. Shen et al.   Cancer Discovery

Mammalian SWI/SNF chromatin remodeling complexes and cancer: Mechanistic insights gained from human genomics

(2015) C. Kadoch et al.   Science Advances

Loss of ARID1A expression sensitizes cancer cells to PI3K- and AKT-inhibition

(2015) Eleftherios P. Samartzis et al.   Oncotarget

ATR Pathway Inhibition Is Synthetically Lethal in Cancer Cells with ERCC1 Deficiency

(2014) K. N. Mohni et al.   CANCER RESEARCH

BRG1/SMARCA4 Inactivation Promotes Non-Small Cell Lung Cancer Aggressiveness by Altering Chromatin Organization

(2014) T. Orvis et al.   CANCER RESEARCH

Molecular Pathways: Targeting the Dependence of Mutant RAS Cancers on the DNA Damage Response

(2014) E. Grabocka et al.   CLINICAL CANCER RESEARCH

Residual Complexes Containing SMARCA2 (BRM) Underlie the Oncogenic Drive of SMARCA4 (BRG1) Mutation

(2014) B. G. Wilson et al.   MOLECULAR AND CELLULAR BIOLOGY

ARID1B is a specific vulnerability in ARID1A-mutant cancers

(2014) Katherine C Helming et al.   NATURE MEDICINE

Targeting RNA polymerase I to treat MYC-driven cancer

(2014) G Poortinga et al.   ONCOGENE

Functional epigenetics approach identifies BRM/SMARCA2 as a critical synthetic lethal target in BRG1-deficient cancers

(2014) G. R. Hoffman et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Personalized synthetic lethality induced by targeting RAD52 in leukemias identified by gene mutation and expression profile

(2013) K. Cramer-Morales et al.   BLOOD

A Synthetic Lethality-Based Strategy to Treat Cancers Harboring a Genetic Deficiency in the Chromatin Remodeling Factor BRG1

(2013) T. Oike et al.   CANCER RESEARCH

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

(2013) Jonathan M. Ostrem et al.   NATURE

Mechanisms of resistance to therapies targeting BRCA-mutant cancers

(2013) Christopher J Lord et al.   NATURE MEDICINE

Survival of the Replication Checkpoint Deficient Cells Requires MUS81-RAD52 Function

(2013) Ivana Murfuni et al.   PLoS Genetics

The GATA2 Transcriptional Network Is Requisite for RAS Oncogene-Driven Non-Small Cell Lung Cancer

(2012) Madhu S. Kumar et al.   CELL

Determination of synthetic lethal interactions in KRAS oncogene-dependent cancer cells reveals novel therapeutic targeting strategies

(2012) Michael Steckel et al.   CELL RESEARCH

Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR

(2012) Anirudh Prahallad et al.   NATURE

Passenger deletions generate therapeutic vulnerabilities in cancer

(2012) Florian L. Muller et al.   NATURE

Synthetic lethality between Rb, p53 and Dicer or miR-17–92 in retinal progenitors suppresses retinoblastoma formation

(2012) David Nittner et al.   NATURE CELL BIOLOGY

Whole-genome sequencing of liver cancers identifies etiological influences on mutation patterns and recurrent mutations in chromatin regulators

(2012) Akihiro Fujimoto et al.   NATURE GENETICS

Functional genomics identifies therapeutic targets for MYC-driven cancer

(2012) M. Toyoshima et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The p53 network: cellular and systemic DNA damage responses in aging and cancer

(2012) H. Christian Reinhardt et al.   TRENDS IN GENETICS

Exploiting Cancer Cell Vulnerabilities to Develop a Combination Therapy for Ras-Driven Tumors

(2011) Thomas De Raedt et al.   CANCER CELL

STK33 Kinase Is Not Essential in KRAS-Dependent Cells-Letter

(2011) S. Frohling et al.   CANCER RESEARCH

Genetic Interactions in Cancer Progression and Treatment

(2011) Alan Ashworth et al.   CELL

Histone H3 trimethylation at lysine 36 is associated with constitutive and facultative heterochromatin

(2011) S. Chantalat et al.   GENOME RESEARCH

Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase

(2011) Christian Frezza et al.   NATURE

Integrated genomic analyses of ovarian carcinoma

(2011) D. Bell et al.   NATURE

A SUMOylation-Dependent Transcriptional Subprogram Is Required for Myc-Driven Tumorigenesis

(2011) J. D. Kessler et al.   SCIENCE

Essential Gene Profiles in Breast, Pancreatic, and Ovarian Cancer Cells

(2011) Richard Marcotte et al.   Cancer Discovery

Specific Killing of Rb Mutant Cancer Cells by Inactivating TSC2

(2010) Binghui Li et al.   CANCER CELL

Combining ATR Suppression with Oncogenic Ras Synergistically Increases Genomic Instability, Causing Synthetic Lethality or Tumorigenesis in a Dosage-Dependent Manner

(2010) O. Gilad et al.   CANCER RESEARCH

Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial

(2010) Andrew Tutt et al.   LANCET

Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial

(2010) M William Audeh et al.   LANCET

ARID1AMutations in Endometriosis-Associated Ovarian Carcinomas

(2010) Kimberly C. Wiegand et al.   NEW ENGLAND JOURNAL OF MEDICINE

Rad52 inactivation is synthetically lethal with BRCA2 deficiency

(2010) Z. Feng et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Oncogenesis Caused by Loss of the SNF5 Tumor Suppressor Is Dependent on Activity of BRG1, the ATPase of the SWI/SNF Chromatin Remodeling Complex

(2009) X. Wang et al.   CANCER RESEARCH

Synthetic Lethal Interaction between Oncogenic KRAS Dependency and STK33 Suppression in Human Cancer Cells

(2009) Claudia Scholl et al.   CELL

A Genome-wide RNAi Screen Identifies Multiple Synthetic Lethal Interactions with the Ras Oncogene

(2009) Ji Luo et al.   CELL

Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1

(2009) David A. Barbie et al.   NATURE

Cdk2 suppresses cellular senescence induced by the c-myc oncogene

(2009) Stefano Campaner et al.   NATURE CELL BIOLOGY

Inhibition of Poly(ADP-Ribose) Polymerase in Tumors fromBRCAMutation Carriers

(2009) Peter C. Fong et al.   NEW ENGLAND JOURNAL OF MEDICINE

Specific synthetic lethal killing of RAD54B-deficient human colorectal cancer cells by FEN1 silencing

(2009) K. J. McManus et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

A Molecule Targeting VHL-Deficient Renal Cell Carcinoma that Induces Autophagy

(2008) Sandra Turcotte et al.   CANCER CELL

Evolutionary plasticity of genetic interaction networks

(2008) Julia Tischler et al.   NATURE GENETICS