AKT1 amplification

The PI3K/AKT/mTOR1 pathway was affected in both the groups as well as the cell cycle regulation pathway. Similarly, the DNA repair gene POLE was found mutated in both vulvar cancer groups.

Importantly, co-targeting N-cadherin and p110α/AKT caused additive reduction in cell migration in vitro and metastases formation in vivo. Together, this study reveals the molecular pathways driven by the PIK3CA aberrations and the exploitable vulnerabilities in PIK3CA-aberrated serous ovarian cancer cells.

P2, N=137, Active, not recruiting, Canadian Cancer Trials Group | Trial completion date: Jan 2024 --> Dec 2024

P2, N=137, Active, not recruiting, Canadian Cancer Trials Group | Trial completion date: Sep 2023 --> Jan 2024

We will use the organoids modeling system -using primary endometrial cells harboring ARID1A mutations- to assess the impact of EO3001 on organoid growth and response to stress conditions and evaluate the effect of EO3001 on cancer metastesis by the ex vivo pulmonary metastasis assay (PuMA). Conclusions Exploiting the vulnerability in reliance on OXPHOS in ARID1A-deficient CCC using EO3001 might represent a promising strategy for the treatment of these patients as well as patients harboring other ARID1A-deficient malignancies.

Exploiting the vulnerability in reliance on OXPHOS in ARID1A-deficient OCCC using EO3001 may represent a promising strategy for the treatment of cancers harboring ARID1A-deficient malignancies.

P2, N=137, Active, not recruiting, Canadian Cancer Trials Group | Trial completion date: Sep 2022 --> Sep 2023

Clinicians who treat patients with endometrial cancer should understand the role of molecular classification in guiding treatment. The goal of this practice statement is to guide appropriate testing, interpretation, and application of molecular information in endometrial cancer.

P4, N=6, Completed, Samsung Medical Center | Unknown status --> Completed | N=25 --> 6

This is the first large-scale whole-genome sequencing for DFSP, and our findings describe the comprehensive genomic landscape, highlighting the molecular complexity and genomic aberrations of DFSP. Our findings also provide novel potential diagnostic and therapeutic targets for this disease. What is already known about this topic? Chromosomal translocation between chromosome 17 and chromosome 22 is the main feature in the pathogenesis of dermatofibrosarcoma protuberans (DFSP). What does this study add? We describe the comprehensive genomic landscape of DFSP, highlighting the molecular complexity and genomic aberrations. Our findings provide novel potential diagnostic and therapeutic targets for this disease. What is the translational message? Our study revealed novel molecular subtypes of DFSP based on genetic mutations, which benefits precision diagnosis. We also found oncogene amplification, including AKT1 and SPHK1, which provides novel potential target molecules for further DFSP treatment. In addition to gene fusion of COL1A1-PDGFβ, we identified a novel gene fusion of SLC2A5-BTBD7 in DFSP, which is a novel potential diagnostic and therapeutic target for this disease.

We review pre-clinical evidence for inhibitors of the main components of the PI3K pathway and highlight past, current and upcoming trials in ovarian cancers for different inhibitors of the pathway. Whilst no inhibitors of the PI3K/AKT/mTOR pathway have thus far advanced to the clinic for the treatment of ovarian cancer, several promising compounds which have the potential to restore platinum sensitivity and improve clinical outcomes for patients are under evaluation and in various phases of clinical trials.

Negative ultraselection warrants further investigation with the aim of maximizing the benefit of EGFR blockade strategies in patients with RAS and BRAF wild-type, microsatellite stable mCRC.