Publications by authors named "D P Sangurdekar"

HRD is common in cancer and can be exploited therapeutically, as it sensitizes cells to DNA-damaging agents. Here, we scored more than 1,300 cancer cell lines for HRD using two different bioinformatic approaches, thereby enabling large-scale analyses that provide insights into the etiology and features of HRD.

View Article and Find Full Text PDF
Article Synopsis
  • Defects in DNA repair pathways, particularly in BRCA1 or BRCA2, contribute to tumor evolution and resistance to therapies like PARP inhibitors, creating vulnerabilities in tumors.
  • Researchers identified USP1 as a key target in BRCA-mutant tumors and developed KSQ-4279, the first selective USP1 inhibitor being tested clinically.
  • The combination of KSQ-4279 and PARP inhibitors showed promise by effectively reducing tumors resistant to PARP treatment, suggesting a new strategy for improving outcomes in patients with HR-deficient tumors.
View Article and Find Full Text PDF

Background And Objectives: Serum neurofilament light chain (sNfL) levels correlate with multiple sclerosis (MS) disease activity, but the dynamics of this correlation are unknown. We evaluated the relationship between sNfL levels and radiologic MS disease activity through monthly assessments during the 24-week natalizumab treatment interruption period in RESTORE (NCT01071083).

Methods: In the RESTORE trial, participants with relapsing forms of MS who had received natalizumab for ≥12 months were randomized to either continue or stop natalizumab and followed with MRI and blood draws every 4 weeks to week 28 and again at week 52 The sNfL was measured, and its dynamics were correlated with the development of gadolinium-enhancing (Gd+) lesions.

View Article and Find Full Text PDF

Objectives: Bruton's tyrosine kinase (BTK) plays a non-redundant signaling role downstream of the B-cell receptor (BCR) in B cells and the receptors for the Fc region of immunoglobulins (FcR) in myeloid cells. Here, we characterise BIIB091, a novel, potent, selective and reversible small-molecule inhibitor of BTK.

Methods: BIIB091 was evaluated and in preclinical models and in phase 1 clinical trial.

View Article and Find Full Text PDF

Objective: To understand how longitudinal serum neurofilament light chain (sNfL) patterns can inform its use as a prognostic biomarker in multiple sclerosis (MS) and evaluate whether sNfL reflects MS disease activity and disease-modifying therapy usage.

Methods: This was a post hoc analysis of longitudinal data and samples from the ADVANCE trial (NCT00906399) of patients with relapsing-remitting MS (RRMS). sNfL was measured every 3 months for 2 years, then every 6 months for 4 years.

View Article and Find Full Text PDF