Yet inevitable therapeutic resistance limits durability of clinical benefit and now defines the central pharmacological challenge of the field, driving development of next-generation DDR inhibitors including saruparib, ART6043, RP-3467, ART0380/alnodesertib, ceralasertib, and peposertib. We propose a biomarker-guided adaptive treatment algorithm integrating longitudinal circulating tumor DNA monitoring, functional RAD51 foci assays, and AI-driven multi-omics integration to enable real-time resistance detection and mechanism-guided therapy switching. This framework advances DDR-targeted oncology from static biomarker selection toward a dynamic, resistance-aware, mechanism-matched therapeutic strategy for patients with metastatic solid tumors.

20 hours ago

Review • Journal • BRCA Biomarker • PARP Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ABCB1 (ATP Binding Cassette Subfamily B Member 1) • RAD51 (RAD51 Homolog A) • STING (stimulator of interferon response cGAMP interactor 1) • TP53BP1 (Tumor Protein P53 Binding Protein 1)

ceralasertib (AZD6738) • saruparib (AZD5305) • peposertib (M3814) • ART6043 • alnodesertib (ART0380)

2ms

ART6043C001: Study of ART6043 in Advanced/Metastatic Solid Tumors Patients (POLKA) (clinicaltrials.gov)

P1/2, N=181, Recruiting, Artios Pharma Ltd | Active, not recruiting --> Recruiting | Trial completion date: Dec 2026 --> Sep 2028 | Trial primary completion date: May 2026 --> Jun 2028

2 months ago

Enrollment open • Trial completion date • Trial primary completion date

HER-2 (Human epidermal growth factor receptor 2) • BRCA (Breast cancer early onset)

Lynparza (olaparib) • ART6043

8ms

ART6043C001: Study of ART6043 in Advanced/Metastatic Solid Tumors Patients (clinicaltrials.gov)

P1/2, N=220, Active, not recruiting, Artios Pharma Ltd | Recruiting --> Active, not recruiting

8 months ago

Enrollment closed

HER-2 (Human epidermal growth factor receptor 2)

Lynparza (olaparib) • ART6043

almost3years

Study of ART6043 in Advanced/Metastatic Solid Tumors Patients (clinicaltrials.gov)

P1/2, N=250, Recruiting, Artios Pharma Ltd | Not yet recruiting --> Recruiting

almost 3 years ago

Enrollment open • Metastases

HER-2 (Human epidermal growth factor receptor 2)

Lynparza (olaparib) • Talzenna (talazoparib) • ART6043

3years

Study of ART6043 in Advanced/Metastatic Solid Tumors Patients (clinicaltrials.gov)

P1/2, N=250, Not yet recruiting, Artios Pharma Ltd

3 years ago

New P1/2 trial • Metastases

HER-2 (Human epidermal growth factor receptor 2)

Lynparza (olaparib) • Talzenna (talazoparib) • ART6043