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Phase I Trial of First-in-Class ATR Inhibitor M6620 (VX-970) as Monotherapy or in Combination With Carboplatin in Patients With Advanced Solid Tumors.
(AMER SOC CLINICAL ONCOLOGY, 2020-06-22)
PURPOSE: Preclinical studies demonstrated that ATR inhibition can exploit synthetic lethality (eg, in cancer cells with impaired compensatory DNA damage responses through ATM loss) as monotherapy and combined with DNA-damaging ...
Phase I Trial of the PARP Inhibitor Olaparib and AKT Inhibitor Capivasertib in Patients with BRCA1/2- and Non-BRCA1/2-Mutant Cancers.
(AMER ASSOC CANCER RESEARCH, 2020-10-01)
Preclinical studies have demonstrated synergy between PARP and PI3K/AKT pathway inhibitors in BRCA1 and BRCA2 (BRCA1/2)-deficient and BRCA1/2-proficient tumors. We conducted an investigator-initiated phase I trial utilizing ...
Intermittent schedules of the oral RAF-MEK inhibitor CH5126766/VS-6766 in patients with RAS/RAF-mutant solid tumours and multiple myeloma: a single-centre, open-label, phase 1 dose-escalation and basket dose-expansion study.
(ELSEVIER SCIENCE INC, 2020-11-01)
BACKGROUND: CH5126766 (also known as VS-6766, and previously named RO5126766), a novel MEK-pan-RAF inhibitor, has shown antitumour activity across various solid tumours; however, its initial development was limited by ...
HER3 expression and MEK activation in non-small-cell lung carcinoma.
(FUTURE MEDICINE LTD, 2021-04-09)
AIM: We explore HER3 expression in lung adenocarcinoma (adeno-NSCLC) and identify potential mechanisms of HER3 expression. MATERIALS & METHODS: Tumor samples from 45 patients with adeno-NSCLC were analyzed. HER3 and HER2 ...
A phase I dose-escalation study of enzalutamide in combination with the AKT inhibitor AZD5363 (capivasertib) in patients with metastatic castration-resistant prostate cancer.
(ELSEVIER, 2020-02-21)
BACKGROUND: Activation of the PI3K/AKT/mTOR pathway through loss of phosphatase and tensin homolog (PTEN) occurs in approximately 50% of patients with metastatic castration-resistant prostate cancer (mCRPC). Recent evidence ...
Molecular and immunological features of a prolonged exceptional responder with malignant pleural mesothelioma treated initially and rechallenged with pembrolizumab.
(BMJ PUBLISHING GROUP, 2020-03-01)
BACKGROUND: This case represents an exceptional response to pembrolizumab in a patient with epithelioid mesothelioma with a further response on rechallenge. CASE PRESENTATION: A 77-year-old woman with advanced epithelioid ...
Research Related Tumour Biopsies in Early-Phase Trials with Simultaneous Molecular Characterisation - a Single Unit Experience.
(Elsevier BV, 2021-01-11)
Early-phase cancer clinical trials are becoming increasingly accessible for patients with advanced cancer who have exhausted standard treatment options and later phase trial options. Many of these trials mandate research ...
Phase 1, dose-escalation study of guadecitabine (SGI-110) in combination with pembrolizumab in patients with solid tumors.
(BMJ PUBLISHING GROUP, 2022-06-01)
BACKGROUND: Data suggest that immunomodulation induced by DNA hypomethylating agents can sensitize tumors to immune checkpoint inhibitors. We conducted a phase 1 dose-escalation trial (NCT02998567) of guadecitabine and ...
Individualized Prediction of Drug Response and Rational Combination Therapy in NSCLC Using Artificial Intelligence-Enabled Studies of Acute Phosphoproteomic Changes.
(AMER ASSOC CANCER RESEARCH, 2022-06-01)
We hypothesize that the study of acute protein perturbation in signal transduction by targeted anticancer drugs can predict drug sensitivity of these agents used as single agents and rational combination therapy. We assayed ...