Understanding resistance mechanisms and expanding the therapeutic utility of PARP inhibitors

10.3390/cancers9080109Cancers9810

Analysis of gene expression signatures identifies prognostic and functionally distinct ovarian clear cell carcinoma subtypes

EBioMedicine50203-21

Identification of serum cytokine clusters associated with outcomes in ovarian clear cell carcinoma

10.1038/s41598-020-75536-1Scientific Reports1011850

Anti-tumor efficacy of Selinexor (KPT-330) in gastric cancer is dependent on nuclear accumulation of p53 tumor suppressor

10.1038/s41598-018-30686-1Scientific Reports811224

Clinical genetic testing outcome with multi-gene panel in Asian patients with multiple primary cancers

10.18632/oncotarget.25769Oncotarget95530649-3066

Tumor molecular profiling of responders and non-responders following pembrolizumab monotherapy in chemotherapy resistant advanced cervical cancer

Optimal treatment for advanced cervical cancer after first line chemotherapy remains undefined. Immune checkpoint inhibition with pembrolizumab, a programmed cell death protein 1(PD-1) inhibitor, is under investigation. We analyzed the micro-environmental and molecular genetic profile of tumors from 4 patients with metastatic cervical cancer treated with off-label second-line pembrolizumab in an effort to identify predictive biomarkers. All patients received 2 mg/kg of pembrolizumab, 3-weekly until disease progression. Immunohistochemistry(IHC) for PD-1, PD-L1, CD3 and CD8, as well as next generation sequencing (NGS) for 50 cancer-related genes were performed on tumor samples. All patients tolerated treatment well with no discontinuation of treatment due to toxicity. One patient experienced dramatic and prolonged partial response, and remains stable on pembrolizumab with a progression free survival (PFS) of 21 months at the time of reporting of this series. Three patients experienced disease progression as best response. In the exceptional responder, there was no tumoral expression of PD-L1, however, combined positive score (CPS) for PD-L1 was 1 and we identified somatic mutations in ERBB4(R612W), PIK3CA(E542K) and RB1(E365K). In 2 patients, despite progressive disease defined by RECIST v1.1, symptom stabilization on pembrolizumab was observed. The tumors of both patients had PD-1 expression in ≥1% of stromal lymphocytes. All patients with response or clinical benefit had CPS for PD-L1 ≥ 1. NGS revealed PIK3CA mutations in 3 tumors. Pembrolizumab is a promising therapeutic option in advanced cervical cancer. Further evaluation of biomarkers may guide optimal patient selection. Keywords: Cervical cancer, Pembrolizumab, Immune checkpoint inhibition, Biomaker

Whole exome sequencing of multi-regional biopsies from metastatic lesions to evaluate actionable truncal mutations using a single-pass percutaneous technique

10.3390/cancers12061599Cancers1261-1

Limb hypothermia for preventing paclitaxel-induced peripheral neuropathy in breast cancer patients: A pilot study

10.3389/fonc.2016.00274Frontiers in Oncology6JAN27

Low Levels of NDRG1 in nerve tissue are predictive of severe paclitaxel-induced neuropathy

10.1371/journal.pone.0164319PLoS ONE1110e016431