News from Kitos
Researchers of Stanford University published this week on Nature Communications a new subtyping of cancer types based on a multi-omic approach. As stated by the authors in the manuscript, "Efforts to distinguish (cancer) subtypes are complicated by the many kinds of genomic changes that contribute to cancer. (...) For example, a copy number change may be relevant only if it causes a gene expression change; gene expression data ignores point mutations that alter the function of the gene product; and point mutations in two different genes may have the same downstream effect, which may become apparent only when also considering methylation or gene expression.". The systematic subtype analysis was carried out across 32 cancer types (TCGA database) using a new algorithm able of incorporating complete genomes and scaling to many data types, termed Cancer Integration via Multikernel LeaRning (CIMLR). Four data types were considered for the analysis: point mutations, copy number alterations, promoter CpG methylation, and gene expression. The subtypes were validated on lower-gliomas, a well-studied example of genomic subtyping, and showed significant differences in patient survival in 23 cancers types. Here, we report some examples of subtypes associated to lower patient survival:
We help our customers in choosing the proper in vitro models for thei projects by providing the molecular features of our cell lines. A proper selection of cell lines in drug discovery is a fundamental step to correlate in vitro to in vivo efficacy and to focus on most aggressive diseases.
Ramazzotti et al., Multi-omic tumor data reveal diversity of molecular mechanisms that correlate with survival. Nat Commun. 2018; 9: 4453. Published online 2018 Oct 26. doi: [10.1038/s41467-018-06921-8].
Link to the open access paper
On November 2 and 3 at Cagliari (IT) and Domusnovas (IT), respectively, the project "A possible development plan for Sulcis-Iglesiente companies: nanotechnologies for the valorization of bee venom as a potential antitumor agent" will be presented.
The project was funded by the Banco di Sardegna Foundation and involves "Domus Api" agricultural company, specialized in honey production and derivatives, the Department of Chemistry and Pharmacy of the University of Sassari, and Nanomater and Kitos Biotech companies. Previous studies have shown the cytotoxic potential of bee venom. The aim of the project is to develop a new formulation that can maximize the effects of poison on cancer cells with minimal effects on normal cells.
Kitos Biotech will evaluate the cytotoxicity of the new formulations on three-dimensional tumor models. Irene Marchesi, CEO of Kitos Biotech, will speak at the conference to illustrate the benefits of 3D cell culture in the study of cancer drugs.
The study involves subjects of the highest scientific profile with different and complementary skills for the execution of the project itself, and we are happy to have been involved. Moreover, the possibility of contributing to the development of the Sulcis area, in the Sardinia region that welcomed us with open arms, believing in us and our value, fills us with pride.
Olaparib significantly improved progression-free survival in patients with advanced BRCA-mutated ovarian cancer. These results were shown on 21th of October at ESMO 2018. The SOLO-1 study is the first to evaluate maintenance therapy with Olaparib, an ADP-ribose polymerase-1 (PARP-1) inhibitor, after platinum-based chemotherapy in advanced ovarian carcinoma with BRCA1/2 mutation.
Of the 391 patients with complete or partial response after chemotherapy and enrolled in the study, 260 received a 300 mg Olaparib tablet twice a day for two years and 130 placebo (one patient did not receive placebo). The analysis of free-progression survival* showed a 70% reduction in the risk of tumor progression or death in Olaparib-treated group. Furthermore, there were no clinically relevant changes in the quality of life, and the dosage was well tolerated with only 12% of patients who discontinued the intake of Olaparib because of its toxicity. Although more time is needed to evaluate benefits in the overall survival**, these results show how treatment is effective and well tolerated, promising to improve current treatments of BRCA mutated ovarian carcinomas.
Original link of the ESMO congress
*Progression free survival: Survival free from tumor progression. The period of time during and after treatment during which a patient lives with the disease but does not get worse.
** Overall survival: Global survival. The period of time between the date of diagnosis or the start of treatment during which the patient is still alive.
On October 16, Kitos Biotech was accepted as an effective member of Assobiotec, the association of bio-industry that operates in Italy. Assobiotec represents 127 companies active in all application fields of biotechnology: pharmaceutical, diagnostics, chemistry, agri-food, plant engineering, instrumental and environmental as well as science and technology parks. Acceptance as an effective member of Assobiotec means the recognition of Kitos Biotech as a company of national relevance in the panorama of Italian biotechnology companies.
Kitos Biotech will become a full member of Federchimica, the National Federation of Chemical Industry, after the second approval step, made up of the Federchimica Presidency Council, which will meet next November 26th.
Link to Assobiotech website
Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer-related death among males, with more than one million diagnosed cases and 350.000 deaths just in 2018. Few days ago, researchers of the National University College of Medicine in Seoul (Korea) published on Nature Communications that CITED2, a transcriptional coregulator of p300/CBP, is uniquely overexpressed in prostate cancer cells, in which it promotes cell migration and metastasis. The authors showed that CITED2 is a target of ERG protein and its over-expression is highly associated to TMPRSS2-ERG gene fusion, which approximatively account for 30% of prostate cancers.
In regard to the mechanism of action, CITED2 binds in the nucleus to nucleolin (NCL), an RNA-binding protein, inducing its cytoplasmic export. Once in the cytoplasm, the CITED2-NCL complex enhances the translation of AKT oncogene, which in turns increases cell migration and metastasis. The metastasis-promoting effect of CITED2 is abolished by CITED2 or NCL knockdown, as well as CITED2-dependent cell migration is almost completely attenuated by pharmacological inhibition of AKT. The identification of this molecular mechanism for metastatization in prostate cancer could bring new opportunities for the development of new prostate cancer treatments.
Global Cancer Observatory, International Agency for Research on Cancer, WHO (http://gco.iarc.fr/)
Seung-Hyun Shin, Ga Young, Mingyu Lee, Jengmin Kang, Hyun-Woo Shin, Yang-Sook Chun & Jong-Wan Park. Aberrant expression of CITED2 promotes prostate cancer metastasis by activating the nucleolin-AKT pathway. Nature Communicationsvolume 9, Article number: 4113 (2018)
Cell proliferation assays are performed by four decades in cancer research to test the anti-proliferative activity of natural products and synthetic compounds in in vitro tumor models such as cell lines. However, current parameters used to quantify growth inhibition lead to a misinterpretation of results based on the exponential, and not linear, proliferation of cells in culture. We recently published in Journal of Cellular Physiology the development and experimental validation of a new parameter for the analysis of growth inhibition in proliferation assays, termed relative doubling capacity, that can be used to properly quantify the anti-proliferative activity of tested compounds in cell cultures and compare drug efficacy between distinct cell models.
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