The Effect of Biomarker Use on the Speed and Duration of Clinical Trials for Cancer Drugs.

BACKGROUND: The purpose of this study was to explore the effects biomarkers have on the duration and speed of clinical trials in oncology. MATERIALS AND METHODS: Clinical trial data was pooled from www.clinicaltrials.gov within the 4 cancer indications of non-small cell lung cancer, breast cancer, melanoma, and colorectal cancer. Heatmaps of clinical timelines were used to display differences in the frequency and timing of clinical trials across trials that used or did not use biomarkers, for all 4 indications. RESULTS: Screening of 8630 clinical trials across the 4 indications yielded 671 unique drugs corresponding to 1224 eligible trials used in our analysis. The constructed heatmaps visually represented that biomarkers did not have an effect on the time gap between trial phases for non-small cell lung cancer and melanoma but did for colorectal and breast cancer trials, reducing the speed of trial timelines. It was also observed that biomarker trials were more often concurrent over shorter periods of time and began later in the timeline for non-small cell lung and colorectal cancers. CONCLUSION: The novel visualization method revealed longer gaps between trial phases, later clinical trial start times, and shorter periods of concurrently run trials for drugs that used biomarkers. The study highlights that biomarker-driven trials might impact drug approval timelines and need to be considered carefully in clinical development plan.

Galenia africana plant extract exhibits cytotoxicity in breast cancer cells by inducing multiple programmed cell death pathways.

Globally, breast cancer is the most common malignancy in women and the second most common cause of cancer-related death among women. There is therefore a need to identify more efficacious therapies for this neoplasm. Galenia africana (Kraalbos) is a perennial shrub found in Southern Africa and is used by the indigenous people to treat various ailments. There has therefore been much interest to establish the scientific basis for the medicinal properties of Kraalbos. This study aimed to investigate and characterise the anti-cancer activity of an ethanolic extract of Kraalbos leaves, KB2, against oestrogen receptor positive (MCF-7) and triple negative (MDA-MB-231) breast cancer cells. LC-MS/MS analyses identified the phytochemicals 7'-hydroxyflavanone, 5',7'-dihydroxyflavanone, 2',4'-dihydroxydihydrochalcone and 2',4'-dihydroxychalcone in KB2. KB2 exhibited an IC50 of 114 µg/ml and 130.5 µg/ml in MCF-7 and MDA-MB-231 cells respectively, selectively inhibited their long-term survival and reduced their migration which correlated with a decrease in EMT markers. It induced oxidative stress (ROS), DNA damage (increased levels of γ-H2AX), and triggered cell cycle arrests in MCF-7 and MDA-MB-231 cells. Importantly, KB2 activated intrinsic (cleaved caspase 9) and extrinsic (cleaved caspase 8) apoptosis, necroptosis (p-RIP3 and the downstream target of the necrosome, pMLKL) and autophagy (LC3II). Co-treatment of the breast cancer cells with KB2 and the autophagy inhibitor bafilomycin A1 resulted in a significant increase in cell viability which suggests that KB2 induced autophagy is a cell death mechanism.