Triple-negative breast cancer (TNBC) is the most aggressive breast tumor subtype and despite treatment advances, still has shorter median overall survival rates and higher recurrence and metastatic rates than other subtypes, due to resistance to chemotherapy.
Triple-negative breast cancer (TNBC) is a highly metastatic and heterogeneous type of tumor, representing 15% of breast cancer cases. To tackle the drug-resistant phenotype of TNBC, effective targeted combinatorial approaches are urgently needed. Writing in EMBO Molecular Medicine journal, researchers from the Centre for Genomic Regulation and collaborators demonstrate that the simultaneous inhibition of lysyl oxidase-like 2 (LOXL2) and bromodomain-containing protein 4 (BRD4) synergistically limits TNBC proliferation in vitro and in vivo.
Glutaminyl-peptide cyclotransferase-like protein (QPCTL) is a modulator of CD47-SIRPα binding and can be targeted to achieve antitumor responses through myeloid checkpoint blockade. At the recent ESMO meeting in Madrid, researchers from Insilico Medicine Inc. reported the preclinical characterization of ISM-8207, a QPCTL inhibitor with activity against triple-negative breast cancer (TNBC) and diffuse large B-cell lymphoma (DLBCL).
Researchers from Birla Institute of Technology & Science, Pilani and Jadavpur University have reported novel HDAC3 inhibitors as potential candidates for the treatment of breast cancer. Synthesis and optimization of a series of pyrazino-hydrazide-based HDAC3 inhibitors led to the characterization of compound [I] as the lead candidate with potent HDAC3 inhibitory activity (IC50=14 nM) and at least 121-fold selectivity.
Previous research has shown high expression of angiotensin-converting enzyme 1 (ACE1) in the triple-negative breast cancer (TNBC) cell line MDA-MB-231, suggesting the potential of ACE1 as a novel target for this disease. In the current study, researchers from Peking University Cancer Hospital presented the discovery of [68Ga]DOTA-BPP, a novel peptide nuclide molecular imaging probe targeting ACE1 for the imaging of TNBC.
Researchers from Chongqing Medical University have reported discovering a novel cyclin-dependent kinase 7 (CDK7) inhibitor, N76-1, which they are investigating as a potential new candidate for the treatment of triple-negative breast cancer (TNBC).
Circle Pharma Inc. has selected CID-078 as its first clinical development candidate. CID-078 is an orally bioavailable macrocycle with dual cyclin A and B inhibitory activity that drives synthetic lethality in multiple tumor types.
Aurora kinases, a group of serine/threonine protein family, comprise Aurora A, B and C members and are involved in the regulation of cell division and mitosis. Aurora A overexpression correlates with poor prognosis and is considered a therapeutic target for cancer treatments, although the clinical development of Aurora kinase inhibitors has been so far limited by excessive safety issues.
The c-Myc oncogene is overexpressed in a significant proportion of human cancers, including difficult-to-treat triple-negative breast cancers (TNBC). In the pursuit of novel anti-TNBC agents, there is a growing interest in ligands that can stabilize c-Myc promoter G-quadruplex (G4), thereby inhibiting c-Myc expression.
