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    DRUG CLASS:

    DDR inhibitor

    Related drugs:
    1m
    SOLARA: Study of Stereotactic Radiosurgery With Olaparib Followed by Durvalumab and Physician's Choice Systemic Therapy in Subjects With Breast Cancer Brain Metastases (clinicaltrials.gov)
    P1/2, N=41, Recruiting, Colette Shen | Trial primary completion date: Sep 2024 --> Nov 2025
    Trial primary completion date • Surgery
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRCA (Breast cancer early onset)
    |
    HER-2 negative • BRCA mutation
    |
    Lynparza (olaparib) • cisplatin • carboplatin • Imfinzi (durvalumab) • gemcitabine • capecitabine • albumin-bound paclitaxel • Halaven (eribulin mesylate)
    2ms
    Study to Assess Safety and Efficacy of AsiDNA in Combination with Olaparib in Participants with Recurrent Solid Tumors (clinicaltrials.gov)
    P1/2, N=3, Completed, Valerio Therapeutics | Recruiting --> Completed | Phase classification: P1b/2 --> P1/2 | N=115 --> 3 | Trial completion date: Apr 2027 --> Oct 2023 | Trial primary completion date: Dec 2026 --> Oct 2023
    Trial completion • Phase classification • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • Pan tumor
    |
    HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor)
    |
    HER-2 positive • HR positive • PGR positive
    |
    Lynparza (olaparib) • AsiDNA (etidaligide)
    3ms
    Avelumab and M6620 for the Treatment of DDR Deficient Metastatic or Unresectable Solid Tumors (clinicaltrials.gov)
    P1/2, N=25, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Sep 2024 --> Dec 2025 | Trial primary completion date: Sep 2024 --> Dec 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • MSH2 (MutS Homolog 2) • CDK12 (Cyclin dependent kinase 12) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • CD4 (CD4 Molecule) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
    |
    Bavencio (avelumab) • berzosertib (M6620)
    3ms
    Inhibition of DDR1 promotes ferroptosis and overcomes gefitinib resistance in non-small cell lung cancer. (PubMed, Biochim Biophys Acta Mol Basis Dis)
    Furthermore, Yfq07 also indirectly induced the ferroptosis of gefitinib-resistant NSCLC cells via SOCS2 triggered inhibition of xCT-GPX4 pathway. In conclusion, our study indicates that DDR1 inhibitor Yfq07 promotes ferroptosis and reverses gefitinib-resistance of NSCLC through DDR1-miR-3648-SOCS2 signalling pathway, which provides insights for targeted therapy of gefitinib-resistant NSCLC and drug developments targeting ferroptosis.
    Journal
    |
    GPX4 (Glutathione Peroxidase 4) • SOCS2 (Suppressor Of Cytokine Signaling 2)
    |
    gefitinib
    4ms
    SOLARA: Study of Stereotactic Radiosurgery With Olaparib Followed by Durvalumab and Physician's Choice Systemic Therapy in Subjects With Breast Cancer Brain Metastases (clinicaltrials.gov)
    P1/2, N=41, Recruiting, Colette Shen | Trial primary completion date: May 2024 --> Aug 2024
    Trial primary completion date • Surgery
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRCA (Breast cancer early onset)
    |
    Lynparza (olaparib) • cisplatin • carboplatin • Imfinzi (durvalumab) • gemcitabine • capecitabine • albumin-bound paclitaxel • Halaven (eribulin mesylate)
    5ms
    Preparation of dearomatized p-coumaric acid derivatives as DNA damage response inhibitors with potent in vitro antitumor effect. (PubMed, ChemMedChem)
    The n-butyl-substituted derivatives 2 and 8 modulated the cell cycle and inhibited the ATR-mediated phosphorylation of checkpoint kinase-1 in MCF-7 cells. As a significant expansion of our previous findings, our results highlight the potential antitumor value of alkyl-substituted graviquinone derivatives.
    Preclinical • Journal
    |
    ABCB1 (ATP Binding Cassette Subfamily B Member 1) • CHEK1 (Checkpoint kinase 1)
    6ms
    Discovery of a prominent dual-target DDR1/EGFR inhibitor aimed DDR1/EGFR-positive NSCLC. (PubMed, Bioorg Chem)
    Demonstrating acceptable pharmacokinetic performance, compound D06 exhibited its anti-tumor activity in NSCLC PC-9/GR xenograft models without apparent toxicity or significant weight loss. These collective results showcase the successful synthesis of a potent dual-targeted inhibitor, suggesting the potential therapeutic efficacy of co-targeting DDR1 and EGFR for DDR1/EGFR-positive NSCLC.
    Journal
    |
    EGFR (Epidermal growth factor receptor)
    7ms
    SADDRIN-1: Sarcomas and DDR-Inhibition; a Combined Modality Study (clinicaltrials.gov)
    P1, N=30, Recruiting, The Netherlands Cancer Institute | N=15 --> 30 | Trial completion date: Mar 2024 --> Jul 2028 | Trial primary completion date: Mar 2024 --> Mar 2026
    Enrollment change • Trial completion date • Trial primary completion date
    |
    Imfinzi (durvalumab) • AZD1390
    8ms
    DAPPER: Basket Combination Study of Inhibitors of DNA Damage Response, Angiogenesis and Programmed Death Ligand 1 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P2, N=90, Active, not recruiting, University Health Network, Toronto | Trial completion date: Dec 2023 --> Jan 2025 | Trial primary completion date: Dec 2023 --> Jan 2025
    Trial completion date • Trial primary completion date • IO biomarker • Pan tumor • Metastases
    |
    HRD (Homologous Recombination Deficiency) • CD4 (CD4 Molecule)
    |
    Lynparza (olaparib) • Imfinzi (durvalumab) • Recentin (cediranib)
    8ms
    The AsiDNA™ decoy mimicking DSBs protects the normal tissue from radiation toxicity through a DNA-PK/p53/p21-dependent G1/S arrest. (PubMed, NAR Cancer)
    Mechanisms comparable to those identified in vitro were detected both in vivo, in the intestine and ex vivo, in precision cut lung slices. Collectively, the results suggest that AsiDNA™ can partially protect healthy tissues from radiation toxicity by triggering a G1/S arrest in normal cells.
    Journal
    |
    CDKN1A (Cyclin-dependent kinase inhibitor 1A)
    |
    AsiDNA (etidaligide)
    8ms
    Study of M1774 in Combination With DNA Damage Response Inhibitor or Immune Checkpoint Inhibitor (DDRiver Solid Tumors 320) (clinicaltrials.gov)
    P1, N=72, Recruiting, EMD Serono Research & Development Institute, Inc. | Trial completion date: Dec 2023 --> May 2026 | Trial primary completion date: Dec 2023 --> Mar 2026
    Trial completion date • Trial primary completion date • Combination therapy • Checkpoint inhibition • IO biomarker • Metastases
    |
    Bavencio (avelumab) • tuvusertib (M1774) • lartesertib (M4076)
    9ms
    CONCORDE: A Platform Study of Novel Agents in Combination With Radiotherapy in NSCLC (clinicaltrials.gov)
    P1, N=200, Recruiting, University of Leeds | Trial completion date: May 2027 --> Mar 2028 | Trial primary completion date: Mar 2023 --> Apr 2025
    Trial completion date • Trial primary completion date • Combination therapy
    |
    Lynparza (olaparib) • Imfinzi (durvalumab) • ceralasertib (AZD6738) • AZD1390 • saruparib (AZD5305)
    12ms
    DNA damage response inhibitors enhance tumour treating fields (TTFields) potency in glioma stem-like cells. (PubMed, Br J Cancer)
    To our knowledge, our findings represent the first report of TTFields applied with clinically approved or in-trial DDRi in GSC models and provides a basis for translational studies toward multimodal DDRi/TTFields-based therapeutic strategies for patients with these currently incurable tumours.
    Journal
    |
    CHEK1 (Checkpoint kinase 1)
    almost1year
    Replicative stress in gastroesophageal cancer is associated with chromosomal instability and sensitivity to DNA damage response inhibitors. (PubMed, iScience)
    We demonstrate that Chk1/2 or Wee1 inhibition combined with SN38/irinotecan shows greater anti-tumor activity in human gastric cancer organoids and an in vivo xenograft mouse model. These findings indicate that specific DDR biomarkers and ploidy abnormalities may predict premalignant progression and response to DDR pathway inhibitors.
    Journal
    |
    TP53 (Tumor protein P53) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
    |
    irinotecan
    1year
    AsiDNA Children, Adolescents and Young Adults (clinicaltrials.gov)
    P1/2, N=8, Terminated, Institut Curie | Trial completion date: Dec 2023 --> Sep 2023 | Suspended --> Terminated | Trial primary completion date: Dec 2023 --> Sep 2023; IDMC recommendations
    Trial completion date • Trial termination • Trial primary completion date
    |
    AsiDNA (etidaligide)
    1year
    Non-small cell lung cancers (NSCLCs) oncolysis using coxsackievirus B5 and synergistic DNA-damage response inhibitors. (PubMed, Signal Transduct Target Ther)
    Meanwhile, no treatment-related deaths due to CV-B5/F and/or inhibitors occurred. Conclusively, our study identifies an oncolytic CV-B5/F and the synergistic effects of inhibitors of DNA-PK or ATM, which is a potential therapy for NSCLCs.
    Journal • IO biomarker
    |
    STING (stimulator of interferon response cGAMP interactor 1)
    1year
    Avelumab and M6620 for the Treatment of DDR Deficient Metastatic or Unresectable Solid Tumors (clinicaltrials.gov)
    P1/2, N=25, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=36 --> 25
    Enrollment closed • Enrollment change • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • MSH2 (MutS Homolog 2) • CDK12 (Cyclin dependent kinase 12) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • CD4 (CD4 Molecule) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
    |
    Bavencio (avelumab) • berzosertib (M6620)
    1year
    TPP1 Inhibits DNA Damage Response and Chemosensitivity in Esophageal Cancer. (PubMed, Crit Rev Eukaryot Gene Expr)
    Strikingly, we found that TPP1 could reduce the chemosensitivity of EC cells to cisplatin, which may have a potential link to clinical chemoresistance. In conclusion, TPP1 regulates the DNA damage response through the ATM/ATR-p53 signaling pathway and chemoresistance and may be a new target for improving the efficacy of chemotherapy in the treatment of EC.
    Journal
    |
    ATR (Ataxia telangiectasia and Rad3-related protein) • TPP1 (Tripeptidyl Peptidase 1)
    |
    ATM expression
    |
    cisplatin
    1year
    Quercetin inhibits DNA damage responses to induce apoptosis via SIRT5/PI3K/AKT pathway in non-small cell lung cancer. (PubMed, Biomed Pharmacother)
    The present study revealed that quercetin directly binds to SIRT5 and inhibits the phosphorylation of PI3K/AKT through the interaction between SIRT5 and PI3K, thus inhibiting the repair process of homologous recombination (HR) and non-homologous end-joining (NHEJ) in NSCLC, which raise mitotic catastrophe and apoptosis. Our study provided a novel mechanism of action of quercetin in the treatment of NSCLC.
    Journal
    |
    SIRT5 (Sirtuin 5)
    over1year
    Pediatric DDR inhibitor combinations: Are WEE1 there yet? (PubMed, Cancer)
    No abstract available
    Journal
    over1year
    Radiosensitization by DNA Damage response inhibitors correlates with Replication stress & HR scores (ESTRO 2023)
    Material and Methods Eight patient derived PDAC cell lines were treated with small molecule inhibitors of ATR (AZD6738 : 20nM - 1µM), PARP (olaparib : 20nM - 1µM) or ATM (AZD1390: 1nM - 100nM) alone and in combination with radiation (0 to 6 Gy). Figure 1 : Survival curves showing radiosensitization of  7 patient derived PDAC cell lines with ATRi(green), ATMi(Blue), PARPi(Red) Figure 2 : Correlation between Replication stress Score and Homologous recombination repair deficiency with ATRi/ATMi  and PARPi radiosensitization Conclusion DDR inhibitors radiosensitized PDAC with the magnitude of radiosensitization depending on Replication Stress and DDR deficiency. These data provide potential therapeutic strategies in the radioresistance setting.
    BRCA Biomarker • PARP Biomarker
    |
    HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
    |
    HRD
    |
    Lynparza (olaparib) • ceralasertib (AZD6738) • AZD1390
    over1year
    Morusinol extracted from Morus alba induces cell cycle arrest and apoptosis via inhibition of DNA damage response in melanoma by CHK1 degradation through the ubiquitin-proteasome pathway. (PubMed, Phytomedicine)
    Morusinol induces CHK1 degradation through the ubiquitin-proteasome pathway, thereby inducing cell cycle arrest, apoptosis and DNA damage response in melanoma. Our study firstly provided a theoretical basis for morusinol to be a candidate drug for clinical treatment of cancer, such as melanoma, alone or combinated with dacarbazine.
    Journal
    |
    CHEK1 (Checkpoint kinase 1)
    |
    dacarbazine
    over1year
    APE1 promotes non-homologous end joining by initiating DNA double-strand break formation and decreasing ubiquitination of artemis following oxidative genotoxic stress. (PubMed, J Transl Med)
    APE1 promotes NHEJ repair by temporally regulating DBS formation and repair following oxidative stress. This knowledge provides new insights into the design of combinatorial therapies and indicates the timing of administration and maintenance of DDR inhibitors for overcoming radio-resistance.
    Journal
    |
    TP53BP1 (Tumor Protein P53 Binding Protein 1)
    almost2years
    Targeted thorium-227 conjugates as treatment options in oncology. (PubMed, Front Med (Lausanne))
    Several alpha radionuclides, including radium-223 (Ra), actinium-225 (Ac), and thorium-227 (Th), have been investigated...A clinical study in hematological malignancy targeting CD22 has demonstrated early signs of activity. Furthermore, pre-clinical studies show additive or synergistic effects when TTCs are combined with established anti-cancer therapies, for example androgen receptor inhibitors (ARI), DNA damage response inhibitors such as poly (ADP)-ribose polymerase inhibitors or ataxia telangiectasia and Rad3-related kinase inhibitors, as well as immune checkpoint inhibitors.
    Review • Journal
    |
    CD22 (CD22 Molecule)
    |
    Xofigo (radium Ra-223 dichloride)
    almost2years
    ENPP1 Immunobiology as a Therapeutic Target. (PubMed, Clin Cancer Res)
    Several ENPP1 inhibitors have shown an immunostimulatory effect and their combination with other therapeutic modalities such as immune checkpoint blockade (ICB), STING activation, DNA damage response (DDR) inhibitors and radiotherapy (RT), represents a promising avenue to boost anti-tumor immune responses and to improve current clinical outcomes in several tumors. This comprehensive review summarizes the current state-of-the art and opens new perspectives for novel treatment strategies.
    Journal
    |
    STING (stimulator of interferon response cGAMP interactor 1) • NT5E (5'-Nucleotidase Ecto) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
    almost2years
    2-Hydroxy-3-methylanthraquinone inhibits homologous recombination repair in osteosarcoma through the MYC-CHK1-RAD51 axis. (PubMed, Mol Med)
    HMA significantly inhibits osteosarcoma proliferation and homologous recombination repair through the MYC-CHK1-RAD51 pathway, which is mediated by the PI3K-AKT signaling pathway. This study investigated the exact mechanism of the anti-osteosarcoma effect of HMA and provided a potential feasible strategy for the clinical treatment of human osteosarcoma.
    Journal
    |
    HRD (Homologous Recombination Deficiency) • RAD51 (RAD51 Homolog A) • CHEK1 (Checkpoint kinase 1) • ANXA5 (Annexin A5)
    almost2years
    Inhibition of ATR Can Target Osimertinib Resistance in EGFR-mutated NSCLC (IASLC-TTLC 2023)
    CONCLUSION Osimertinib-resistant cell line models have differential sensitivity to ATR inhibitors, but not to other inhibitors of DNA repair or to platinum chemotherapy. The basis for this specific sensitivity to ATR inhibitors remains under investigation, but may form the basis of new approaches to target TKI-resistant, EGFR-driven lung tumors.
    PARP Biomarker
    |
    EGFR (Epidermal growth factor receptor) • CHEK1 (Checkpoint kinase 1)
    |
    EGFR mutation
    |
    Tagrisso (osimertinib)
    almost2years
    DAPPER: Basket Combination Study of Inhibitors of DNA Damage Response, Angiogenesis and Programmed Death Ligand 1 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P2, N=90, Active, not recruiting, University Health Network, Toronto | Trial completion date: Oct 2022 --> Dec 2023 | Trial primary completion date: Oct 2022 --> Dec 2023
    Trial completion date • Trial primary completion date • IO biomarker • Pan tumor • Metastases
    |
    HRD (Homologous Recombination Deficiency) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
    |
    Lynparza (olaparib) • Imfinzi (durvalumab) • Recentin (cediranib)
    almost2years
    Chlorin e6-induced photodynamic effect facilitates immunogenic cell death of lung cancer as a result of oxidative endoplasmic reticulum stress and DNA damage. (PubMed, Int Immunopharmacol)
    In summary, Ce6 PDT could produce ROS under certain conditions, which leads to ER stress that promotes CRT translocation to the cell membrane, and the resulting DNA damage causes the expression and release of nuclear HMGB1 and HSP90, thereby enhancing the immunogenicity of lung cancer. This current study elucidates the mechanism of PDT in ameliorating the immunogenicity of lung cancer, providing a rationale for PDT in regulating the immune microenvironment for the treatment of malignant tumors.
    Journal
    |
    HMGB1 (High Mobility Group Box 1) • HSPA5 (Heat Shock Protein Family A (Hsp70) Member 5) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)
    almost2years
    Interference with pathways activated by topoisomerase inhibition alters the surface expression of PD-L1 and MHC I in colon cancer cells. (PubMed, Oncol Lett)
    Additionally, adaptive tolerance to topoisomerase inhibition caused altered cell cycle response, and reduced the expression levels of both PD-L1 and MHC I on both microsatellite instable and stable colon cancer cell lines. Therefore, targeted modulation of DDR pathways, PD-L1, MHC I or other immune regulators in colon cancer cells may make them more visible to immune cells and enable rational combination of conventional therapy with immunotherapy.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression
    almost2years
    Clinicopathological Characteristics of Lung Carcinomas with Loss of KDM5D Expression (USCAP 2023)
    Notably, phase II clinical trials of ATR inhibitor M6620 (VX-970) for small cell lung cancer have shown durable responses...Notably, phase II clinical trials of ATR inhibitor M6620 (VX-970) for small cell lung cancer have shown durable responses... Our results revealed that approximately one-fourth of lung carcinomas in males, including all histologic types, exhibited KDM5D expression loss, which is potentially sensitive to ATR inhibitors. DDR pathway is a promising therapeutic target in lung carcinoma, especially for male patients with lung carcinomas harboring no targetable genomic alterations .
    Clinical • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • KDM5D (Lysine Demethylase 5D)
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    PD-L1 expression • PD-L1 overexpression
    |
    berzosertib (M6620)
    almost2years
    Chinese medicine formula 'Baipuhuang Keli' inhibits triple-negative breast cancer by hindering DNA damage repair via MAPK/ERK pathway. (PubMed, J Ethnopharmacol)
    Collectively, we proved that BPH is a potential anticancer Chinese herbal formula for TNBC in the manner of in vitro and in vivo experiments.
    Journal
    |
    EGF (Epidermal growth factor)
    almost2years
    Targeting the DNA Damage Response Machinery for Lung Cancer Treatment. (PubMed, Pharmaceuticals (Basel))
    This review article sheds light on the different DNA repair pathways and some of the inhibitors targeting the proteins involved in the DNA damage response (DDR) machinery, such as ataxia telangiectasia and Rad3-related protein (ATR), DNA-dependent protein kinase (DNA-PK), and poly-ADP-ribose polymerase (PARP). In addition, the current status of DDR inhibitors in clinical settings and future perspectives are discussed.
    Review • Journal • PARP Biomarker
    |
    ATR (Ataxia telangiectasia and Rad3-related protein)
    almost2years
    ncRNA-mediated overexpression of ubiquitin-specific proteinase 13 contributes to the progression of prostate cancer via modulating AR signaling, DNA damage repair and immune infiltration. (PubMed, BMC Cancer)
    Taken together, our study revealed a key role of USP13 in contributing to PCa progression by participating in multiple oncogenic signaling pathways, the DNA damage response and the immunosuppressive tumor microenvironment. Targeting USP13 may inhibit tumor growth and provide additional benefits in cooperation with DDR inhibitors and immunotherapy.
    Journal • IO biomarker • Epigenetic controller
    |
    TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • USP13 (Ubiquitin Specific Peptidase 13)
    almost2years
    Nuclear factor Nrf2 promotes glycosidase OGG1 expression by activating the AKT pathway to enhance leukemia cell resistance to cytarabine. (PubMed, J Biol Chem)
    Furthermore, the use of OGG1 inhibitor TH5487 could partially reverse the inhibitory effect of up-regulated Nrf2 on leukemia cell apoptosis. Mechanistically, Nrf2-OGG1 axis-mediated AML resistance might be achieved by activating the AKT signaling pathway to regulate downstream apoptotic proteins. Thus, this study reveals a novel mechanism of Nrf2 promoting drug resistance in leukemia, which may provide a potential therapeutic target for the treatment of drug-resistant/refractory leukemia.
    Journal
    |
    OGG1 (8-Oxoguanine DNA glycosylase)
    |
    cytarabine
    almost2years
    LncRNA CEBPA-DT promotes liver cancer metastasis through DDR2/β-catenin activation via interacting with hnRNPC. (PubMed, J Exp Clin Cancer Res)
    Our results suggested that CEBPA-DT promoted HCC metastasis through DDR2/β-catenin mediated activation of Snail1 via interaction with hnRNPC, indicating that the CEBPA-DT-hnRNPC-DDR2/β-catenin axis may be used as a potential therapeutic target for HCC treatment.
    Journal
    |
    CEBPA (CCAAT Enhancer Binding Protein Alpha) • DDR2 (Discoidin domain receptor 2) • SNAI1 (Snail Family Transcriptional Repressor 1) • HNRNPC (Heterogeneous Nuclear Ribonucleoprotein C)
    almost2years
    Molecular Targeted Therapy in Oncology Focusing on DNA Repair Mechanisms. (PubMed, Arch Med Res)
    In this review we will describe the state of the art of this interesting mechanism and explain the options for treatment based on these alterations. Moreover, many clinical trials are currently underway exploring better treatment options for dMMR and HRD patients with different solid tumours.
    Review • Journal • PARP Biomarker • IO biomarker
    |
    HRD (Homologous Recombination Deficiency)
    |
    MSI-H/dMMR
    almost2years
    Glutathione-sensitive nanoparticles enhance the combined therapeutic effect of checkpoint kinase 1 inhibitor and cisplatin in prostate cancer. (PubMed, APL Bioeng)
    Furthermore, we show that the glutathione-targeted Cys8E nanoparticles we synthesized, which have high drug-loading capacity, remarkable stability, and satisfactory release efficiency, enhanced the therapeutic efficacy of this treatment and reduced the required dosages of these drugs both in vitro and in vivo. Overall, we propose combination therapy of cisplatin and AZD7762 for PCa and facilitate it using Cys8E nanoparticles, which allow for better drug loading release, higher release efficiency, and more accurate tumor-targeting efficacy.
    Journal
    |
    CHEK1 (Checkpoint kinase 1)
    |
    cisplatin • AZD-7762
    almost2years
    H3.3-G34 mutations impair DNA repair and promote cGAS/STING-mediated immune responses in pediatric high-grade glioma models. (PubMed, J Clin Invest)
    We treated H3.3-G34R pHGG-bearing mice with a combination of radiotherapy (RT) and DNA damage response inhibitors (DDRi) (i.e., the blood-brain barrier-permeable PARP inhibitor pamiparib and the cell-cycle checkpoint CHK1/2 inhibitor AZD7762), and these combinations resulted in long-term survival for approximately 50% of the mice. Long-term survivors developed immunological memory, preventing pHGG growth upon rechallenge. These results demonstrate that DDRi and STING agonists in combination with RT induce immune-mediated therapeutic efficacy in G34-mutant pHGG.
    Journal • PARP Biomarker
    |
    STING (stimulator of interferon response cGAMP interactor 1) • CGAS (Cyclic GMP-AMP Synthase)
    |
    Partruvix (pamiparib) • AZD-7762
    2years
    ATM mutations profile in pancreatic ductal adenocarcinoma assessed by targeted ultra-deep next generation sequencing of FNA-genomic DNA and cfDNA samples (APA-Pancreatic 2022)
    FNA-genomic DNA and cfDNA targeted NGS ultra-deep sequencing provides complementary results to generate an ATM gene mutations profile that could be relevant for diagnosis, prognosis, and personalized treatment, in non-resectable PDAC patients. p.(Cys728Tyr) somatic mutation and p.(Asp1853Asn) germline mutation are important candidate SNPs for further research.
    Next-generation sequencing • PARP Biomarker
    |
    ATM (ATM serine/threonine kinase)
    |
    ATM mutation
    2years
    PLX038: a long-acting topoisomerase I inhibitor with robust anti-tumor activity in ATM deficient tumors and potent synergy with PARP inhibitors. (PubMed, Mol Cancer Ther)
    A patient with an ATM mutated breast cancer treated with PLX038 and the PARP inhibitor rucaparib achieved rapid, symptomatic, and radiographic complete response lasting twelve months. Single agent PLX038 or PLX038 in combination with DNA damage response inhibitors are novel therapeutic paradigms for patients with ATM-loss cancers.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • ATM (ATM serine/threonine kinase)
    |
    Rubraca (rucaparib) • PLX038