CCNE1 mutation

Lastly, a drug screening identified four candidate reagents commonly effective to all PDOs. Collectively, we showed that multiple PDOs could help reproduce the spatial diversity of a tumor and serve as a valuable resource in UCS research in many respects.

The combination of HER2 amplification and PD-L1 expression in Chinese patients with GC could stratify the total populations into several subgroups with distinctive genomic and immune landscapes, which should be considered when making personalized treatment decisions.

P1, N=66, Recruiting, National Cancer Institute (NCI) | Phase classification: P1b --> P1 | Initiation date: Nov 2023 --> Feb 2024

Across solid tumors, alterations associated with sensitivity to CDK4/6 inhibitors varied widely in frequency. Though the frequency of alterations in CDK4/6 inhibitor resistance genes was generally low, identifying such patients may be critical for decisions regarding the use of CDK4/6 inhibitors.

P1b, N=66, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting | Initiation date: May 2023 --> Nov 2023

Conclusions This exploratory study showed that HRD testing on cytological specimens from EOC ascites is feasible but standardized pre-analytical procedures are required to ensure adequate samples for the analysis. Ascites might represent a valid alternative for early BRCA1/2 and HRD status evaluation in women with EOC when tissue samples are inadequate/insufficient.

P1b, N=66, Suspended, National Cancer Institute (NCI) | Not yet recruiting --> Suspended

Our observations provide additional evidence that MLAs have a Müllerian origin and characterise mesonephric-like carcinosarcomas in which chondroid elements appear to be characteristic. In reporting these findings, we provide recommendations for distinction between a mesonephric-like carcinosarcoma and a MLA with a spindle cell component.

Although more and more patients with ovarian cancer are undergoing tumor-based next-generation sequencing to identify genetic mutations in their tumors, the benefits of such testing are not well established. In a group of over 400 patients with ovarian cancer who underwent tumor-based next-generation sequencing in the course of their treatment, nearly all patients had one or more genetic alterations detected, and one out of four patients had a mutation that qualified them for a personalized treatment option.

Somatic sequencing is warranted to identify patients of this subset of HGSOC, and understanding the co-amplifications and co-mutations is essential so that they are targeted for optimal survival outcomes.

These models, designated ST4565C, ST4565D, STM148B, STM148C, STM148D, and ST4480B/EHR were developed and characterized for receptor expression, genomics, and drug sensitivities toward chemotherapies and targeted agents including T-DXd, T-DM1, and margetuximab. ST4565C/D was established from a patient with ER+/HER2+, metastatic BC who was T-DXd treatment naïve. ST4565C was collected post chemo- and HER2-targeted therapies; ST4565D was collected following eribulin/margetuximab... We established and characterized six breast XPDX models representing innate or acquired resistance to T-DXd. These models are valuable tools in understanding resistance mechanisms and in developing novel therapies for T-DXd-resistant patients.

P1b, N=66, Not yet recruiting, National Cancer Institute (NCI)

Molecular profiles and TME are associated with OS. TME differs per profile, with higher immune cell densities showing a favorable OS, even within the profiles. HGSOC does not reflect one entity but comprises different entities based on molecular profiles and TME.

Of the 4 cases with detailed clinical history (median follow-up period 8 months), 3 developed distant metastatic disease (one of which died of disease); one case remained free of disease 3?years following surgical excision. In conclusion, we describe a heterogeneous series of MAML2-rearranged undifferentiated malignant epithelioid neoplasms, a small subset of which may overlap with a recently described MIFS variant with YAP1::MAML2 fusions, further expanding the clinicopathologic spectrum of mesenchymal neoplasms with recurrent MAML2 gene rearrangements.

For patients with cervical cancer, tumor NGS and IHC profile may help identify potential candidate for targeted therapy and immunotherapy.

RP2D was ola 300mg BID D1-5, 15-19 + ada 300mg OD D8-12, 22-26; Q28 days. Planned expansion cohorts include (1) pts with BRCA1/2m tumors with intrinsic PARPi resistance and (2) pts with DDR mutated tumors with acquired PARPi resistance.

Molecular profiles and TME are associated with OS. TME differs per profile, with higher immune cell densities showing a favorable OS, even within the profiles. HGSOC does not reflect one entity but comprises different entities based on molecular profile and TME which could assist with patienttailored treatment in the future.