While DDR inhibitors hold great potential as standalone therapies or in combination with chemotherapy, immunotherapy, and radiation, challenges persist, including overlapping toxicities and damage to healthy tissues. This review aims to illuminate the rapidly advancing field of DDR-based targeted cancer therapies, emphasizing their potential to revolutionize treatment approaches and improve patient outcomes.

3 months ago

Journal • BRCA Biomarker • PARP Biomarker • IO biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog A) • CHEK1 (Checkpoint kinase 1)

4ms

PHOENIX DDR/Anti-PD-L1 Trial: A Pre-surgical Window of Opportunity and Post-surgical Adjuvant Biomarker Study of DNA Damage Response Inhibition With or Without Anti-PD-L1 Immunotherapy in Patients With Neoadjuvant Treatment Resistant Residual Triple Negative Breast Cancer (clinicaltrials.gov)

P2, N=119, Recruiting, Institute of Cancer Research, United Kingdom | N=81 --> 119 | Trial completion date: Dec 2025 --> Jun 2029 | Trial primary completion date: Mar 2023 --> Dec 2026

4 months ago

Enrollment change • Trial completion date • Trial primary completion date • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)

HER-2 negative • ER negative

Prosigna™ Breast Cancer Prognostic Gene Signature Assay

Lynparza (olaparib) • Imfinzi (durvalumab) • ceralasertib (AZD6738)

6ms

Biomimetic nanoplatforms for combined DDR2 inhibition and photothermal therapy in dense breast cancer treatment. (PubMed, Biomaterials)

M@P-WIs effectively overcome this resistance mechanism by producing complete CAF depletion alongside tumor ablation. Our findings demonstrate that integrating CAF-targeted stromal modulation with PTT synergistically enhances therapeutic efficacy, offering a promising strategy for treating stroma-rich, aggressive tumors.

6 months ago

Journal

TGFB1 (Transforming Growth Factor Beta 1) • DDR2 (Discoidin domain receptor 2)

6ms

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 primary completion date: Dec 2025 --> Nov 2024

6 months ago

Trial primary completion date

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)

7ms

Study of Tuvusertib (M1774) in Combination With DNA Damage Response Inhibitor or Immune Checkpoint Inhibitor (DDRiver Solid Tumors 320) (clinicaltrials.gov)

P1, N=123, Recruiting, EMD Serono Research & Development Institute, Inc. | N=72 --> 123

7 months ago

Enrollment change • Checkpoint inhibition • IO biomarker

Bavencio (avelumab) • tuvusertib (M1774) • lartesertib (M4076)

8ms

CONCORDE: A Platform Study of Novel Agents in Combination With Radiotherapy in NSCLC (clinicaltrials.gov)

P1, N=200, Recruiting, University of Leeds | Trial primary completion date: Apr 2025 --> Mar 2026

8 months ago

Trial primary completion date

Lynparza (olaparib) • Imfinzi (durvalumab) • ceralasertib (AZD6738) • AZD1390 • saruparib (AZD5305)

8ms

DAPPER: Study of DNA Damage, Angiogenesis, and PD-L1 Inhibitors in Advanced Solid Tumors (clinicaltrials.gov)

P2, N=90, Active, not recruiting, University Health Network, Toronto | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2025 --> Jan 2026

8 months ago

Trial completion date • Trial primary completion date

HRD (Homologous Recombination Deficiency)

Lynparza (olaparib) • Imfinzi (durvalumab) • Recentin (cediranib)

10ms

Explanatory review on DDR inhibitors: their biological activity, synthetic route, and structure-activity relationship. (PubMed, Mol Divers)

We have also compiled the evolutionary development status of DDR inhibitors according to their chemical classes, biological activity, selectivity, and structure-activity relationship. From biological activity analysis, it was revealed that compounds 64a (selectivity: DDR1) and 103a (selectivity: DDR2) were the most potent candidates with excellent activity with IC50 values of 4.67 and 3.2 nM, respectively.

10 months ago

Review • Journal

DDR2 (Discoidin domain receptor 2)

12ms

Ion channel modulator DPI-201-106 significantly enhances antitumor activity of DNA damage response inhibitors in glioblastoma. (PubMed, Neurooncol Adv)

Combination treatment of DPI-201-106 with the CHK1 inhibitor prexasertib or the PARP inhibitor niraparib demonstrated synergistic effects in multiple patient-derived glioblastoma cells both in vitro and in intracranial xenograft mouse models, extending survival of glioblastoma-bearing mice. DPI-201-106 enhances the efficacy of DDR inhibitors to reduce glioblastoma growth. As these drugs have already been clinically tested in humans, repurposing DPI-201-106 in novel combinatorial approaches will allow for rapid translation into the clinic.

12 months ago

Journal • PARP Biomarker

ANXA5 (Annexin A5)

Zejula (niraparib) • prexasertib (ACR-368)

1year

REVOCAN: Safety and Efficacy of AsiDNATM, a DNA Repair Inhibitor, Administered Intravenously in Addition to PARP Inhibitors in Patients With Relapsed Platinum Sensitive Ovarian Cancer Already Treated With PARP Inhibitors Since at Least 6 Months (clinicaltrials.gov)

P1/2, N=13, Terminated, Gustave Roussy, Cancer Campus, Grand Paris | N=26 --> 13 | Trial completion date: Oct 2023 --> Apr 2024 | Recruiting --> Terminated | Trial primary completion date: Oct 2023 --> Apr 2024; Treatment availability issue: The manufacturer of AsiDNA™ decided to cease production to develop an improved version, and the contract ensuring access to this molecule has expired.

1 year ago

Enrollment change • Trial completion date • Trial termination • Trial primary completion date

BRCA (Breast cancer early onset) • MUC16 (Mucin 16, Cell Surface Associated)

Lynparza (olaparib) • Zejula (niraparib) • Rubraca (rucaparib) • AsiDNA (etidaligide)

1year

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

1 year ago

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)