Development of patient derived organoids for cancer drug screening applications.

Cancer is a disease characterised by abnormal cell growth that can invade or spread to other regions of the body. Organoids are three-dimensional ex vivo tissue cultures made from embryonic stem cells, induced pluripotent stem cells, progenitor cells or tissue that serve as a physiological model for cancer research. These are designed to recapitulate the in vivo properties of tumours. Importantly, effective recapitulation of the structure of tissues and function is believed to predict patient response, allowing for the creation of personalised therapy in a timely manner that may be used in the clinic. This Review discusses the pre-clinical model and different types of human organoids as models for the development of high throughput drug screening and also aims to highlight how organoids are shaping the future of cancer research.

Molecular landscape and subtype-specific therapeutic response of nasopharyngeal carcinoma revealed by integrative pharmacogenomics.

Nasopharyngeal carcinoma (NPC) is a malignant head and neck cancer type with high morbidity in Southeast Asia, however the pathogenic mechanism of this disease is poorly understood. Using integrative pharmacogenomics, we find that NPC subtypes maintain distinct molecular features, drug responsiveness, and graded radiation sensitivity. The epithelial carcinoma (EC) subtype is characterized by activations of microtubule polymerization and defective mitotic spindle checkpoint related genes, whereas sarcomatoid carcinoma (SC) and mixed sarcomatoid-epithelial carcinoma (MSEC) subtypes exhibit enriched epithelial-mesenchymal transition (EMT) and invasion promoting genes, which are well correlated with their morphological features. Furthermore, patient-derived organoid (PDO)-based drug test identifies potential subtype-specific treatment regimens, in that SC and MSEC subtypes are sensitive to microtubule inhibitors, whereas EC subtype is more responsive to EGFR inhibitors, which is synergistically enhanced by combining with radiotherapy. Through combinational chemoradiotherapy (CRT) screening, effective CRT regimens are also suggested for patients showing less sensitivity to radiation. Altogether, our study provides an example of applying integrative pharmacogenomics to establish a personalized precision oncology for NPC subtype-guided therapies.

Pharmacoinformatic Approach to Explore the Antidote Potential of Phytochemicals on Bungarotoxin from Indian Krait, Bungarus caeruleus.

Venomous reptiles especially serpents are well known for their adverse effects after accidental conflicts with humans. Upon biting humans these serpents transmit arrays of detrimental toxins with diverse physiological activities that may either lead to minor symptoms such as dermatitis and allergic response or highly severe symptoms such as blood coagulation, disseminated intravascular coagulation, tissue injury, and hemorrhage. Other complications like respiratory arrest and necrosis may also occur. Bungarotoxins are a group of closely related neurotoxic proteins derived from the venom of kraits (Bungarus caeruleus) one of the six most poisonous snakes in India whose bite causes respiratory paralysis and mortality without showing any local symptoms. In the current study, by employing various pharmacoinformatic approaches, we have explored the antidote properties of 849 bioactive phytochemicals from 82 medicinal plants which have already shown antidote properties against various venomous toxins. These herbal compounds were taken and pharmacoinformatic approaches such as ADMET, docking and molecular dynamics were employed. The three-dimensional modelling approach provides structural insights on the interaction between bungarotoxin and phytochemicals. In silico simulations proved to be an effective analytical tools to investigate the toxin-ligand interaction, correlating with the affinity of binding. By analyzing the results from the present study, we proposed nine bioactive phytochemical compounds which are, 2-dodecanol, 7-hydroxycadalene, indole-3-(4'-oxo)butyric acid, nerolidol-2, trans-nerolidol, eugenol, benzene propanoic acid, 2-methyl-1-undecanol, germacren-4-ol can be used as antidotes for bungarotoxin.