DNA Damage Response Inhibitors in Cholangiocarcinoma: Current Progress and Perspectives

Article Chemistry, Multidisciplinary

BAP1 loss augments sensitivity to BET inhibitors in cancer cells

Yu-yan Xu et al.

Summary: The study reveals that BAP1 loss makes cells more vulnerable to BET inhibitors, leading to a more potent suppressive effect on the transcription of various proliferation-related genes, especially MYC.

ACTA PHARMACOLOGICA SINICA (2022)

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Review Biochemistry & Molecular Biology

Therapeutic Targeting of DNA Damage Response in Cancer

Wonyoung Choi et al.

Summary: The DNA damage response (DDR) pathway plays a critical role in maintaining genome stability and defects in this pathway are associated with cancer. Exploiting vulnerabilities in this pathway has led to successful anticancer therapies, such as PARP inhibitors. This review discusses key elements of the DDR pathway and the development of pharmacologic inhibitors. It also highlights the importance of biomarker studies and combination strategies in optimizing clinical benefits.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Review Oncology

Hallmarks of Cancer: New Dimensions

Douglas Hanahan

Summary: The concept of the hallmarks of cancer is a tool for simplifying the complexity of cancer phenotypes and genotypes into basic principles. This article proposes phenotypic plasticity and disrupted differentiation as distinct hallmark capabilities, and discusses nonmutational epigenetic reprogramming and polymorphic microbiomes as enabling characteristics. Additionally, the importance of senescent cells in the tumor microenvironment is highlighted. The integrative concept of the hallmarks of cancer helps in understanding the mechanisms of cancer development and applying that knowledge to cancer medicine.

CANCER DISCOVERY (2022)

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Review Oncology

The new insight of treatment in Cholangiocarcinoma

Yuhang Li et al.

Summary: Cholangiocarcinoma is a rare but highly malignant tumor with increasing incidence and death rate. Treatment options include surgery, radiotherapy, and chemotherapy, with targeted therapy and immunotherapy showing potential. Clinical trials for cholangiocarcinoma are underway.

JOURNAL OF CANCER (2022)

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Review Oncology

The role of PARP inhibitors in gastrointestinal cancers

Daire Hanna et al.

Summary: The use of BRCA mutations as biomarkers for sensitivity to targeted drugs and platinum agents is well documented in breast and gynecological cancers. Recent studies have shown that DDR targeted therapies extend to other deficiencies within the HR pathway. However, gastrointestinal cancers lag behind in personalized treatment and current methods for determining PARP-inhibitor sensitivity are based on analogies from other cancer types. Therefore, it is important to better understand the implications of DDR alterations in gastrointestinal cancers.

CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY (2022)

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Article Oncology

Inhibition of WEE1 Potentiates Sensitivity to PARP Inhibitor in Biliary Tract Cancer

Hye-Rim Seo et al.

Summary: The study demonstrates that the combination therapy of olaparib and AZD1775 has significant anti-tumor effects against BTC, particularly showing a more potent effect in reducing tumor growth. This combination therapy has the potential to be further developed for clinical application in BTC patients.

CANCER RESEARCH AND TREATMENT (2022)

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Article Gastroenterology & Hepatology

DNA damage repair as a target in pancreatic cancer: state-of-the-art and future perspectives

Lukas Perkhofer et al.

Summary: Complex rearrangement patterns and mitotic errors are characteristics of most PDAC, caused by DNA double-strand breaks and defective DNA repair pathways. DSB repair pathways, such as HR, play a crucial role in maintaining genomic integrity, and deficiencies in DDR pathways like BRCA1 and BRCA2 are common in both inherited and sporadic PDAC, leading to potential vulnerabilities to new therapeutic interventions. The POLO trial with olaparib showed promising results in PDAC patients with germline BRCA1/2 mutations, suggesting a potential for improved outcomes in this subgroup.

GUT (2021)

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Article Oncology

Dual Screen for Efficacy and Toxicity Identifies HDAC Inhibitor with Distinctive Activity Spectrum for BAP1-Mutant Uveal Melanoma

Jeffim N. Kuznetsoff et al.

Summary: This study successfully identified a compound, quisinostat, through cell viability assays and mouse models, that targets mutations in tumor suppressor genes and shows potential therapeutic effects on various cancers such as uveal melanoma.

MOLECULAR CANCER RESEARCH (2021)

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Article Oncology

A first-in-man phase 1 study of the DNA-dependent protein kinase inhibitor peposertib (formerly M3814) in patients with advanced solid tumours

Mark T. J. van Bussel et al.

Summary: This phase 1 trial aimed to determine the maximum-tolerated dose and recommended phase 2 dose of peposertib, a DNA-dependent protein kinase inhibitor, in patients with advanced solid tumors. Peposertib was well-tolerated and showed modest efficacy in unselected tumors, with the recommended dose declared as 400 mg twice daily. Further studies are ongoing with peposertib/chemo-radiation combinations.

BRITISH JOURNAL OF CANCER (2021)

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Article Pharmacology & Pharmacy

The antiproliferative effects of ataxia-telangiectasia mutated and ATM- and Rad3-related inhibitions and their enhancements with the cytotoxicity of DNA damaging agents in cholangiocarcinoma cells

Benchamart Moolmuang et al.

Summary: Inhibition of ATM and ATR kinases enhanced the cytotoxic effects of DNA damaging agents in cholangiocarcinoma cells, showing stronger cytotoxic activity in some cell lines. Different DNA damaging drugs induced distinct phases of the cell cycle in cholangiocarcinoma cells.

JOURNAL OF PHARMACY AND PHARMACOLOGY (2021)

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Article Medicine, General & Internal

Adavosertib plus gemcitabine for platinum-resistant or platinum-refractory recurrent ovarian cancer: a double-blind, randomised, placebo-controlled, phase 2 trial

Stephanie Lheureux et al.

LANCET (2021)

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Review Pharmacology & Pharmacy

Alterations of DNA damage response pathway: Biomarker and therapeutic strategy for cancer immunotherapy

Minlin Jiang et al.

Summary: Genomic instability is a crucial feature of cancer development, enabled by alterations in DNA damage response pathways that promote malignant transformation. These changes impact the immune system, generate new antigens, and interact with various signaling pathways, potentially serving as targets and biomarkers in cancer immunotherapy.

ACTA PHARMACEUTICA SINICA B (2021)

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Article Oncology

Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Hyuna Sung et al.

Summary: The global cancer burden in 2020 saw an estimated 19.3 million new cancer cases and almost 10.0 million cancer deaths. Female breast cancer surpassed lung cancer as the most commonly diagnosed cancer, while lung cancer remained the leading cause of cancer death. These trends are expected to rise in 2040, with transitioning countries experiencing a larger increase compared to transitioned countries due to demographic changes and risk factors associated with globalization and a growing economy. Efforts to improve cancer prevention measures and provision of cancer care in transitioning countries will be crucial for global cancer control.

CA-A CANCER JOURNAL FOR CLINICIANS (2021)

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Review Pharmacology & Pharmacy

Investigational PARP inhibitors for the treatment of biliary tract cancer: spotlight on preclinical and clinical studies

Rutika Mehta et al.

Summary: Prospective clinical data with PARPis in the treatment of BTCs are limited. The potential combination of PARPis and IDH1 inhibitors or immune checkpoint inhibitors in clinical trials is interesting because of the potential synergistic preclinical data. There are other possible combinations including those drugs that target the angiogenesis or STAT3 pathways. An enhanced understanding of acquired resistance to PARPis is necessary to progress the use of these agents in clinical trials.

EXPERT OPINION ON INVESTIGATIONAL DRUGS (2021)

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Review Pharmacology & Pharmacy

Targeting the tumor microenvironment in cholangiocarcinoma: implications for therapy

Corentin Louis et al.

Summary: Cholangiocarcinoma (CCA) is a rare and deadly cancer with limited effective treatments, leading to a need for new therapeutic strategies targeting the tumor microenvironment (TME). Single-cell RNA sequencing of the stroma in CCA provides a critical functional characterization of TME, paving the way for immunotherapies and other innovative treatments. Combining TME-targeted treatments with cytotoxic chemotherapy may yield better results, requiring the development of biomarkers to define patient populations for each strategy.

EXPERT OPINION ON THERAPEUTIC TARGETS (2021)

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Article Oncology

Phase II Study of the WEE1 Inhibitor Adavosertib in Recurrent Uterine Serous Carcinoma

Joyce F. Liu et al.

Summary: Adavosertib monotherapy showed encouraging and durable evidence of activity in women with USC, with a progression-free survival rate of 47.1% at 6 months and an objective response rate of 29.4%. The study suggests that Adavosertib may be an effective treatment option for USC patients and further investigation is warranted.

JOURNAL OF CLINICAL ONCOLOGY (2021)

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Review Oncology

Practical considerations in screening for genetic alterations in cholangiocarcinoma

T. S. Bekaii-Saab et al.

Summary: Cholangiocarcinoma (CCA) is associated with poor outcomes due to aggressive disease progression, late diagnosis, and limited effectiveness of standard chemotherapy. Molecular profiling has revealed diverse genomic alterations as oncogenic drivers, with TP53, CDKN2A/B, and KRAS being the most common genetic alterations in CCA. Intrahepatic CCA (iCCA) and extrahepatic CCA (eCCA) differ substantially in the frequency of genetic alterations, including actionable alterations like IDH1 mutations and FGFR2 rearrangements. Targeted therapies for these alterations provide opportunities for improved treatment plans tailored to the individual patient's genetic signature.

ANNALS OF ONCOLOGY (2021)

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Review Biochemistry & Molecular Biology

DNA damage response inhibitors: An avenue for TNBC treatment

Juan Jin et al.

Summary: DDR is essential for the survival of TNBC, as TNBC exhibits replication stress and DNA damage requiring DDR for maintenance. Aberrant genetic alterations in DDR pathways in TNBC make it more susceptible to DDR inhibitors.

BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER (2021)

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Article Oncology

Safety, Antitumor Activity, and Biomarker Analysis in a Phase I Trial of the Once-daily Wee1 Inhibitor Adavosertib (AZD1775) in Patients with Advanced Solid Tumors

Naoko Takebe et al.

Summary: This study identified the recommended phase II dose of once-daily adavosertib and observed activity in patients with ovarian or endometrial carcinoma. Some patients exhibited baseline CCNE1 mRNA overexpression, which may be associated with response.

CLINICAL CANCER RESEARCH (2021)

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Article Oncology

Efficacy of adavosertib therapy against anaplastic thyroid cancer

Yu-Ling Lu et al.

Summary: Adavosertib, a Wee1 inhibitor, showed significant inhibition on cell growth and induced G2/M phase accumulation and apoptosis in anaplastic thyroid cancer cells. Combination therapy with Adavosertib and other drugs demonstrated synergistic effects in inhibiting tumor growth, with no apparent toxicity in mice. These findings suggest the promise of Adavosertib for the treatment of anaplastic thyroid cancer patients.

ENDOCRINE-RELATED CANCER (2021)

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Review Immunology

Targeting DNA Repair Response Promotes Immunotherapy in Ovarian Cancer: Rationale and Clinical Application

Hongyu Xie et al.

Summary: Combining DDR inhibitors with ICI therapy in ovarian cancer can enhance local antigen release, promote systemic antitumor immune responses, and potentially improve clinical outcomes for patients with ovarian cancer. This combination therapy strategy is based on the interconnectivity between DDR pathway deficiency and immune response, and it is supported by available clinical trials and potential predictive biomarkers.

FRONTIERS IN IMMUNOLOGY (2021)

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Article Oncology

WEE1 inhibition reverses trastuzumab resistance in HER2-positive cancers

Mei-Hua Jin et al.

Summary: This study revealed higher PD-L1 expression in trastuzumab-resistant HER2-positive cancer cells and showed that blocking PD-L1 could reverse resistance to trastuzumab. Co-targeting HER2 and WEE1 was found to overcome resistance to trastuzumab in HER2-positive cancers, offering potential therapeutic options for patients.

GASTRIC CANCER (2021)

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Article Gastroenterology & Hepatology

Genetic Determinants of Outcome in Intrahepatic Cholangiocarcinoma

Thomas Boerner et al.

Summary: Genetic alterations in iCCA, including TP53, KRAS, and CDKN2A mutations, are associated with poorer prognosis, especially in advanced disease, independent of clinical and pathological variables. Combining targeted tumor sequencing with clinical variables may help identify patient subgroups with poor outcomes, regardless of treatment strategy.

HEPATOLOGY (2021)

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Review Oncology

Biliary Tract Cancers: Treatment Updates and Future Directions in the Era of Precision Medicine and Immuno-Oncology

Ashish Manne et al.

Summary: Recent advancements in precision medicine have made it possible to identify new molecular markers for BTCs, including epigenetic changes and non-DNA markers, providing hope for improved diagnosis and treatment outcomes.

FRONTIERS IN ONCOLOGY (2021)

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Review Oncology

Targeting DNA Damage Repair for Immune Checkpoint Inhibition: Mechanisms and Potential Clinical Applications

Wei Sun et al.

Summary: DDR pathways are crucial for maintaining genomic integrity and have implications for response to ICIs. Among these pathways, mismatch repair is a well-recognized predictive biomarker for ICIs. The combination of agents targeting DDR pathways with ICIs shows promise for cancer treatment.

FRONTIERS IN ONCOLOGY (2021)

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Article Oncology

Identification of Mutator-Derived Alternative Splicing Signatures of Genomic Instability for Improving the Clinical Outcome of Cholangiocarcinoma

Zijing Lin et al.

Summary: This study investigated the relationship between alternative splicing events and cholangiocarcinoma, constructing a prognostic signature with six AS events. The research identified CDK11A as a negative regulator of survival-associated AS events and found that patients with high AS risk score may benefit more from immunotherapy.

FRONTIERS IN ONCOLOGY (2021)

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Article Oncology

Phase 1 study of the ATR inhibitor berzosertib in combination with cisplatin in patients with advanced solid tumours

Geoffrey Shapiro et al.

Summary: The study assessed the safety, tolerability, pharmacokinetics, and efficacy of berzosertib plus cisplatin in patients with advanced solid tumors. The combination therapy was well tolerated and showed preliminary clinical activity in some patients, supporting further evaluation in a Phase 2 setting.

BRITISH JOURNAL OF CANCER (2021)

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Article Oncology

ATR inhibition amplifies antitumor effects of olaparib in biliary tract cancer

Ah-Rong Nam et al.

Summary: Olaparib in combination with ATR inhibitor has shown significant anti-tumor effects in biliary tract cancer, leading to DNA strand breaks and downregulation of PD-L1, YAP, CXCR2, and CXCR4, providing a potential therapeutic approach for patients with BTC.

CANCER LETTERS (2021)

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Article Biochemistry & Molecular Biology

In Vitro Evaluation of Rigosertib Antitumoral and Radiosensitizing Effects against Human Cholangiocarcinoma Cells

Alessio Malacrida et al.

Summary: Cholangiocarcinoma is the most common cancer of the biliary tract, and surgical resection is currently the only potentially curative option with low survival rates. Research shows that Rigosertib may be a potential therapeutic option for nonresectable patients with cholangiocarcinoma.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Meeting Abstract Oncology

IDH1 and IDH2 Driven Intrahepatic Cholangiocarcinoma (IHCC): A comprehensive genomic and immune profiling study.

Shalini Makawita et al.

JOURNAL OF CLINICAL ONCOLOGY (2021)

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Review Oncology

Locoregional Treatments in Cholangiocarcinoma and Combined Hepatocellular Cholangiocarcinoma

Matteo Renzulli et al.

Summary: Cholangiocarcinoma and combined hepatocellular cholangiocarcinoma are aggressive primary malignancies with liver resection as the main treatment modality. Locoregional therapies can provide local tumor control and increase chances of survival.

CANCERS (2021)

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Article Oncology

Niraparib Suppresses Cholangiocarcinoma Tumor Growth by Inducing Oxidative and Replication Stress

Vladimir Bezrookove et al.

Summary: Cholangiocarcinoma is a rare and aggressive tumor with limited treatment options, but PARP inhibitors show promise as a novel therapy for CCA. Mutations in DNA damage response genes make these tumors susceptible to PARP inhibitors, which can suppress cancer cell viability and induce apoptosis.

CANCERS (2021)

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Review Oncology

Interventional Treatment for Cholangiocarcinoma

Hang Li et al.

Summary: Cholangiocarcinoma is the second most common type of primary liver malignancy, with surgical resection being the preferred treatment for eligible patients. Interventional treatment has become an acceptable palliative option for unresectable CCA, providing locoregional control, symptom relief, and improved quality of life.

FRONTIERS IN ONCOLOGY (2021)

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Article Oncology

DNA Damage Response and Repair Gene Alterations Increase Tumor Mutational Burden and Promote Poor Prognosis of Advanced Lung Cancer

Jiawei Dai et al.

Summary: DDR gene alterations in lung cancer without oncogenic drivers are positively associated with high TMB, and specific DDR gene alterations tend to associate with worse progression-free survival to initial chemotherapy.

FRONTIERS IN ONCOLOGY (2021)

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Article Oncology

A Phase 1b Trial of Prexasertib in Combination with Standard-of-Care Agents in Advanced or Metastatic Cancer

Kathleen N. Moore et al.

Summary: This study demonstrated that prexasertib can be effectively combined with cisplatin, cetuximab, and 5-fluorouracil. The schedule of administration is crucial in determining the tolerability and feasibility of combining prexasertib with these standard agents. Hematologic toxicity was the most common adverse event and dose-limiting factor in these combinations. Insights gained from this study will guide future combination strategies for the development of prexasertib and next-generation CHK1 inhibitors.

TARGETED ONCOLOGY (2021)

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Review Oncology

Genetic aberrations in DNA repair pathways: a cornerstone of precision oncology in prostate cancer

Rebeca Lozano et al.

Summary: Several studies have shown that defects in DNA damage response and repair (DDR) genes are present in a significant proportion of prostate cancer patients, particularly mutations in BRCA2 which are associated with increased risk and aggressiveness of the disease. Certain DDR gene aberrations may confer sensitivity to specific drug therapies, while other defects could indicate a potential benefit from immune checkpoint inhibition for patients.

BRITISH JOURNAL OF CANCER (2021)

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Article Medicine, Research & Experimental

Mutational spectrum and precision oncology for biliary tract carcinoma

Jianzhen Lin et al.

Summary: The study revealed extensive genomic diversity and heterogeneity among biliary tract carcinoma (BTC) patients, with different gene mutations having varying impacts on patient prognosis. Personalized targeted therapies showed significant efficacy in patients with potentially actionable targets, providing a basis for further clinical trials.

THERANOSTICS (2021)

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News Item Biotechnology & Applied Microbiology

PKMYT1: a forgotten member of the WEE1 family

Christopher R. M. Asquith et al.

NATURE REVIEWS DRUG DISCOVERY (2020)

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Article Oncology

Global trends in intrahepatic and extrahepatic cholangiocarcinoma incidence from 1993 to 2012

Andrea A. Florio et al.

CANCER (2020)

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Article Oncology

The combination of BET and PARP inhibitors is synergistic in models of cholangiocarcinoma

Samuel C. Fehling et al.

CANCER LETTERS (2020)

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Article Cell Biology

Systematic expression analysis of WEE family kinases reveals the importance of PKMYT1 in breast carcinogenesis

Yu Liu et al.

CELL PROLIFERATION (2020)

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Review Cell Biology

Nuclear PARPs and genome integrity

Kameron Azarm et al.

GENES & DEVELOPMENT (2020)

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Review Pharmacology & Pharmacy

Targeting ATR as Cancer Therapy: A new era for synthetic lethality and synergistic combinations?

Alice Bradbury et al.

PHARMACOLOGY & THERAPEUTICS (2020)

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Review Biochemistry & Molecular Biology

ATM, ATR and DNA-PKcs kinases-the lessons from the mouse models: inhibition ≠ deletion

Demis Menolfi et al.

CELL AND BIOSCIENCE (2020)

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Article Oncology

Inhibition of ATR Increases the Sensitivity to WEE1 Inhibitor in Biliary Tract Cancer

Ah-Rong Nam et al.

CANCER RESEARCH AND TREATMENT (2020)

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Review Biochemistry & Molecular Biology

Biomarker-Guided Development of DNA Repair Inhibitors

James M. Cleary et al.

MOLECULAR CELL (2020)

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Article Multidisciplinary Sciences

Targeting therapeutic vulnerabilities with PARP inhibition and radiation in IDH-mutant gliomas and cholangiocarcinomas

Yuxiang Wang et al.

SCIENCE ADVANCES (2020)

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Review Cell Biology

Role of Histone Deacetylases in Carcinogenesis: Potential Role in Cholangiocarcinoma

Kishor Pant et al.

CELLS (2020)

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Article Medicine, General & Internal

Olaparib for Metastatic Castration-Resistant Prostate Cancer

J. de Bono et al.

NEW ENGLAND JOURNAL OF MEDICINE (2020)

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Article Oncology

Effect of food on the pharmacokinetics of the WEE1 inhibitor adavosertib (AZD1775) in patients with advanced solid tumors

Mats Nagard et al.

CANCER CHEMOTHERAPY AND PHARMACOLOGY (2020)

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Review Oncology

Combined PARP Inhibition and Immune Checkpoint Therapy in Solid Tumors

Florent Peyraud et al.

CANCERS (2020)

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Article Oncology

Phase I Trial of First-in-Class ATR Inhibitor M6620 (VX-970) as Monotherapy or in Combination With Carboplatin in Patients With Advanced Solid Tumors

Timothy A. Yap et al.

JOURNAL OF CLINICAL ONCOLOGY (2020)

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Article Oncology

Molecular profile of BRCA-mutated biliary tract cancers

Gilbert Spizzo et al.

ESMO OPEN (2020)

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Review Oncology

Advances in synthetic lethality for cancer therapy: cellular mechanism and clinical translation

Win Topatana et al.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2020)

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Review Oncology

A WEE1 family business: regulation of mitosis, cancer progression, and therapeutic target

Andrea Ghelli Luserna di Rora et al.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2020)

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Article Oncology

Analysis of differentially expressed mRNAs and the prognosis of cholangiocarcinoma based on TCGA database

Kun Wang et al.

TRANSLATIONAL CANCER RESEARCH (2020)

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Article Medicine, General & Internal

Molecular Profiling in Daily Clinical Practice: Practicalities in Advanced Cholangiocarcinoma and Other Biliary Tract Cancers

Angela Lamarca et al.

JOURNAL OF CLINICAL MEDICINE (2020)

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Review Cell Biology

PARP Inhibitors: Clinical Relevance, Mechanisms of Action and Tumor Resistance

Maddison Rose et al.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2020)

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Review Oncology

Epigenetic based synthetic lethal strategies in human cancers

Aiai Gao et al.

BIOMARKER RESEARCH (2020)

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Article Oncology

Case Report: BAP1 Mutation and RAD21 Amplification as Predictive Biomarkers to PARP Inhibitor in Metastatic Intrahepatic Cholangiocarcinoma

Francesco Sabbatino et al.

FRONTIERS IN ONCOLOGY (2020)

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Article Oncology

Intrahepatic Cholangiocarcinoma: Genomic Heterogeneity Between Eastern and Western Patients

Jingyu Cao et al.

JCO PRECISION ONCOLOGY (2020)

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Article Biochemistry & Molecular Biology

ATM Inhibitor Suppresses Gemcitabine-Resistant BTC Growth in a Polymerase θ Deficiency-Dependent Manner

Yi-Ru Pan et al.

BIOMOLECULES (2020)

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Review Pharmacology & Pharmacy

DNA-PK in human malignant disorders: Mechanisms and implications for pharmacological interventions

Michaela Medova et al.

PHARMACOLOGY & THERAPEUTICS (2020)

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Review Biochemistry & Molecular Biology

DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer

Rui-Xue Huang et al.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2020)

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Review Oncology

Biliary tract cancer and genomic alterations in homologous recombinant deficiency: exploiting synthetic lethality with PARP inhibitors

Daniel H. Ahn et al.

CHINESE CLINICAL ONCOLOGY (2020)

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Article Oncology

OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physician's choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer

M. E. Robson et al.

ANNALS OF ONCOLOGY (2019)

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Review Oncology

PARP Inhibitors: Extending Benefit Beyond BRCA-Mutant Cancers

Patrick G. Pilie et al.

CLINICAL CANCER RESEARCH (2019)

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Article Biochemistry & Molecular Biology

Poly(ADP-ribosyl)ation by PARP1: reaction mechanism and regulatory proteins

Elizaveta E. Alemasova et al.

NUCLEIC ACIDS RESEARCH (2019)

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Article Oncology

Alterations in DNA Damage Repair Genes in Primary Liver Cancer

Jianzhen Lin et al.

CLINICAL CANCER RESEARCH (2019)

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Review Genetics & Heredity

Inflammation-induced DNA damage, mutations and cancer

Jennifer Kay et al.

DNA REPAIR (2019)

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Article Medicine, General & Internal

Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer

Talia Golan et al.

NEW ENGLAND JOURNAL OF MEDICINE (2019)

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Review Genetics & Heredity

Perspectives on PARPs in S Phase

Hana Hanzlikova et al.

TRENDS IN GENETICS (2019)

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Review Oncology

DNA-PK as an Emerging Therapeutic Target in Cancer

Ismail S. Mohiuddin et al.

FRONTIERS IN ONCOLOGY (2019)

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Article Multidisciplinary Sciences

BAP1 regulates epigenetic switch from pluripotency to differentiation in developmental lineages giving rise to BAP1-mutant cancers

Jeffim N. Kuznetsov et al.

SCIENCE ADVANCES (2019)

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Review Cell Biology

Cellular Stress Responses in Radiotherapy

Wanyeon Kim et al.

CELLS (2019)

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Article Oncology

Therapeutic relevance of targeted sequencing in management of patients with advanced biliary tract cancer: DNA damage repair gene mutations as a predictive biomarker

Heejung Chae et al.

EUROPEAN JOURNAL OF CANCER (2019)

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Article Oncology

Therapeutic Targeting of the DNA Damage Response Using an ATR Inhibitor in Biliary Tract Cancer

Ah-Rong Nam et al.

CANCER RESEARCH AND TREATMENT (2019)

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Review Biochemistry & Molecular Biology

ROS and the DNA damage response in cancer

Upadhyayula Sai Srinivas et al.

REDOX BIOLOGY (2019)

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Review Cell Biology

The Enigmatic Function of PARP1: From PARylation Activity to PAR Readers

Tatiana Kamaletdinova et al.

CELLS (2019)

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Review Gastroenterology & Hepatology

Immunobiology of cholangiocarcinoma

Emilien Loeuillard et al.

JHEP REPORTS (2019)

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Article Oncology

Genomic and Functional Approaches to Understanding Cancer Aneuploidy

Alison M. Taylor et al.

CANCER CELL (2018)

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Article Biochemistry & Molecular Biology

Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal

Samra Turajlic et al.

CELL (2018)

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Article Biochemistry & Molecular Biology

The Importance of Poly(ADP-Ribose) Polymerase as a Sensor of Unligated Okazaki Fragments during DNA Replication

Hana Hanzlikova et al.

MOLECULAR CELL (2018)

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Article Multidisciplinary Sciences

Chromosomal instability drives metastasis through a cytosolic DNA response

Samuel F. Bakhoum et al.

NATURE (2018)

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Article Genetics & Heredity

Genome doubling shapes the evolution and prognosis of advanced cancers

Craig M. Bielski et al.

NATURE GENETICS (2018)

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Article Oncology

Protein kinase, membrane-associated tyrosine/threonine 1 is associated with the progression of colorectal cancer

Dongjun Jeong et al.

ONCOLOGY REPORTS (2018)

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Article Cell Biology

Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas

Theo A. Knijnenburg et al.

CELL REPORTS (2018)

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Article Oncology

PARP inhibitor olaparib sensitizes cholangiocarcinoma cells to radiation

Yize Mao et al.

CANCER MEDICINE (2018)

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Review Oncology

Biliary Tract Cancer: State of the Art and potential role of DNA Damage Repair

Angela Lamarca et al.

CANCER TREATMENT REVIEWS (2018)

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Article Medicine, General & Internal

Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation

Jennifer K. Litton et al.

NEW ENGLAND JOURNAL OF MEDICINE (2018)

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Article Oncology

Survival analysis of genome-wide profiles coupled with Connectivity Map database mining to identify potential therapeutic targets for cholangiocarcinoma

Peng Lin et al.

ONCOLOGY REPORTS (2018)

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Article Oncology

Long-term efficacy, tolerability and overall survival in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer treated with maintenance olaparib capsules following response to chemotherapy

Michael Friedlander et al.

BRITISH JOURNAL OF CANCER (2018)

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Article Medicine, General & Internal

Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer

K. Moore et al.

NEW ENGLAND JOURNAL OF MEDICINE (2018)

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Review Oncology

Dancing with the DNA damage response: next-generation anti-cancer therapeutic strategies

Anna Minchom et al.

THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY (2018)

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Review Oncology

Combining DNA damaging therapeutics with immunotherapy: more haste, less speed

Jessica S. Brown et al.

BRITISH JOURNAL OF CANCER (2018)

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Article Oncology

Radiotherapy-Activated Cancer-Associated Fibroblasts Promote Tumor Progression through Paracrine IGF1R Activation

Joke Tommelein et al.

CANCER RESEARCH (2018)

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Review Oncology

Targeting DNA Repair in Cancer : Beyond PARP Inhibitors

Jessica S. Brown et al.

CANCER DISCOVERY (2017)

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Article Oncology

Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial

Eric Pujade-Lauraine et al.

LANCET ONCOLOGY (2017)

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Article Oncology

DNA Damage Induces a Secretory Program in the Quiescent TME that Fosters Adverse Cancer Phenotypes

Luis Gomez-Sarosi et al.

MOLECULAR CANCER RESEARCH (2017)

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Article Oncology

Tumor Mutational Burden as an Independent Predictor of Response to Immunotherapy in Diverse Cancers

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MOLECULAR CANCER THERAPEUTICS (2017)

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MOLECULAR CELL (2017)

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Chromosome 1q21.3 amplification is a trackable biomarker and actionable target for breast cancer recurrence

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NEW ENGLAND JOURNAL OF MEDICINE (2017)

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ONCOLOGIST (2017)

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

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IDH -Mutant Tumors Vulnerable to PARP Inhibition

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Tuning Chromosomal Instability to Optimize Tumor Fitness

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PLOS ONE (2017)

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Endogenous DNA Damage as a Source of Genomic Instability in Cancer

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CELL (2017)

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INVESTIGATIONAL NEW DRUGS (2016)

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Next-Generation Sequencing Survey of Biliary Tract Cancer Reveals the Association Between Tumor Somatic Variants and Chemotherapy Resistance

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Effects of Anticancer Drugs on Chromosome Instability and New Clinical Implications for Tumor-Suppressing Therapies

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Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

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WORLD JOURNAL OF GASTROENTEROLOGY (2016)

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Olaparib Monotherapy in Patients With Advanced Cancer and a Germline BRCA1/2 Mutation

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Numerical chromosomal instability mediates susceptibility to radiation treatment

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Genome-wide Profiling of Genetic Synthetic Lethality Identifies CDK12 as a Novel Determinant of PARP1/2 Inhibitor Sensitivity

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