METHODS: Purification and structure elucidation were carried out by chromatographic and spectroscopic techniques, respectively. MTT and trypan blue exclusion methods were performed to study the cytotoxic activity. Antibacterial activity was conducted by disc diffusion and microdilution methods, whereas antioxidant activities were done by ferric thiocyanate method and DPPH radical scavenging.

RESULTS: The phytochemical study led to the isolation of α,β-mangostin and cycloart-24-en-3β-ol. α-Mangostin exhibited cytotoxic activity against HSC-3 cells with an IC(50) of 0.33 μM. β- and α-mangostin showed activity against K562 cells with IC(50) of 0.40 μM and 0.48 μM, respectively. α-Mangostin was active against Gram-positive bacteria, Staphylococcus aureus (S. aureus) and Bacillus anthracis (B. anthracis) with inhibition zone and MIC value of (19 mm; 0.025 mg/mL) and (20 mm; 0.013 mg/mL), respectively. In antioxidant assay, α-mangostin exhibited activity as an inhibitor of lipid peroxidation.

Methods: Three semi-synthetic series of compounds (C1-4, P1-4, and G1-4) were prepared and evaluated biologically as potential dual epidermal growth factor receptor (EGFR) and COX-2 inhibitors. The main phenolic constituents of Amaranthus spinosus L. (p-coumaric, caffeic and gallic) acids have been isolated and subsequently subjected to diazo coupling with various amines to get novel three chemical scaffolds with potential anticancer activities.

Results: Compounds C4 and G4 showed superior inhibitory activity against EGFR (IC50: 0.9 and 0.5 µM, respectively) and displayed good COX-2 inhibition (IC50: 4.35 and 2.47 µM, respectively). Moreover, the final compounds were further evaluated for their cytotoxic activity against human colon cancer (HT-29), pancreatic cancer (PaCa-2), human malignant melanoma (A375), lung cancer (H-460), and pancreatic ductal cancer (Panc-1) cell lines. Interestingly, compounds C4 and G4 exhibited the highest cytotoxic activity with average IC50 values of 1.5 µM and 2.8 µM against H-460 and Panc-1, respectively. The virtual docking study was conducted to gain proper understandings of the plausible-binding modes of target compounds within EGFR and COX-2 binding sites.

METHODS: A parallel RCT was conducted in two hospitals in Malaysia, where 129 CML patients were randomised to MMS or control (usual care) groups using a stratified 1:1 block randomisation method. The 6-month MMS included three face-to-face medication use reviews, CML and TKI-related education, two follow-up telephone conversations, a printed information booklet and two adherence aids. Medication adherence (primary outcome), molecular responses and health-related quality of life (HRQoL) scores were assessed at baseline, 6th and 12th month. Medication adherence and HRQoL were assessed using medication possession ratio and the European Organisation for Research and Treatment in Cancer questionnaire (EORTC_QLQ30_CML24) respectively.

RESULTS: The MMS group (n = 65) showed significantly higher adherence to TKIs than the control group (n = 64) at 6th month (81.5% vs 56.3%; p = 0.002), but not at 12th month (72.6% vs 60.3%; p = 0.147). In addition, a significantly higher proportion of participants in the MMS group achieved major molecular response at 6th month (58.5% vs 35.9%; p = 0.010), but not at 12th month (66.2% vs 51.6%; p = 0.092). Significant deep molecular response was also obtained at 12th month (24.6% vs 10.9%; p = 0.042). Six out of 20 subscales of EORTC-QLQ30-CML24 were significantly better in the MMS group.

CONCLUSIONS: The MMS improved CML patients' adherence to TKI as well as achieved better clinical outcomes.

RESULTS: We developed DeSigN, a web-based tool for predicting drug efficacy against cancer cell lines using gene expression patterns. The algorithm correlates phenotype-specific gene signatures derived from differentially expressed genes with pre-defined gene expression profiles associated with drug response data (IC50) from 140 drugs. DeSigN successfully predicted the right drug sensitivity outcome in four published GEO studies. Additionally, it predicted bosutinib, a Src/Abl kinase inhibitor, as a sensitive inhibitor for oral squamous cell carcinoma (OSCC) cell lines. In vitro validation of bosutinib in OSCC cell lines demonstrated that indeed, these cell lines were sensitive to bosutinib with IC50 of 0.8-1.2 μM. As further confirmation, we demonstrated experimentally that bosutinib has anti-proliferative activity in OSCC cell lines, demonstrating that DeSigN was able to robustly predict drug that could be beneficial for tumour control.

METHODS: Treatment-naive patients with EGFR-mutated advanced NSCLC were randomized one-to-one to lazertinib (240 mg/d) or gefitinib (250 mg/d). Patients with asymptomatic or stable CNS metastases were included if any planned radiation, surgery, or steroids were completed more than 2 weeks before randomization. For patients with CNS metastases confirmed at screening or subsequently suspected, CNS imaging was performed every 6 weeks for 18 months, then every 12 weeks. End points assessed by blinded independent central review and Response Evaluation Criteria in Solid Tumors version 1.1 included intracranial progression-free survival, intracranial objective response rate, and intracranial duration of response.

RESULTS: Of the 393 patients enrolled in LASER301, 86 (lazertinib, n = 45; gefitinib, n = 41) had measurable and or non-measurable baseline CNS metastases. The median intracranial progression-free survival in the lazertinib group was 28.2 months (95% confidence interval [CI]: 14.8-28.2) versus 8.4 months (95% CI: 6.7-not reached [NR]) in the gefitinib group (hazard ratio = 0.42, 95% CI: 0.20-0.89, p = 0.02). Among patients with measurable CNS lesions, the intracranial objective response rate was numerically higher with lazertinib (94%; n = 17) versus gefitinib (73%; n = 11, p = 0.124). The median intracranial duration of response with lazertinib was NR (8.3-NR) versus 6.3 months (2.8-NR) with gefitinib. Tolerability was similar to the overall LASER301 population.