Principles of Cancer Therapy: Oncogene and Non-oncogene Addiction
Cancer is a complex collection of distinct genetic diseases united by common hallmarks. Here, we expand upon the classic hallmarks to include the stress phenotypes of tumorigenesis. We describe a conceptual framework of how oncogene and non-oncogene addictions contribute to these hallmarks and how they can be exploited through stress sensitization and stress overload to selectively kill cancer cells. In particular, we present evidence for a large class of non-oncogenes that are essential for cancer cell survival and present attractive drug targets. Finally, we discuss the path ahead to therapeutic discovery and provide theoretical considerations for combining orthogonal cancer therapies. [1]
Mechanism of met oncogene activation
The met oncogene activated in vitro by treatment of a human osteogenic sarcoma (HOS) cell line with N-methyl-N′-nitronitrosoguanidine (MNNG) is related to the tyrosine kinase gene family. Probes from the met oncogene locus recognize two distinct transcripts of 9.0 kb and 10.0 kb which are independently expressed in a cell-type-specific fashion. While the met proto-oncogene locus expresses the 9.0 kb RNA and maps to human chromosome 7q21–31, the locus expressing the 10.0 kb RNA, ( tpr; translocated promoter region) maps to human chromosome 1. Both MNNG-HOS cells and met NIH 3T3 transformants express a novel 5.0 kb RNA which represents a hybrid transcript with 5′ sequences derived from tpr and 3′ sequences from the met proto-oncogene. Treating HOS cells in vitro with MNNG, a known clastogenic carcinogen, resulted in fusion of two chromosomally disparate loci, met and tpr, generating the active met oncogene. [2]
A microRNA polycistron as a potential human oncogene
To date, more than 200 microRNAs have been described in humans; however, the precise functions of these regulatory, non-coding RNAs remains largely obscure. One cluster of microRNAs, the mir–17–92 polycistron, is located in a region of DNA that is amplified in human B-cell lymphomas1. Here we compared B-cell lymphoma samples and cell lines to normal tissues, and found that the levels of the primary or mature microRNAs derived from the mir–17–92 locus are often substantially increased in these cancers. [3]
Oncogenic Human Papillomavirus Detection in Penile Lichen Sclerosus: An Update
Aims: Aim of this study was to better address a possible association of human papillomavirus (HPV) infection with penile lichen sclerosus (LS).
Study Design: Paraffin-embedded penile biopsies obtained from adult patients with genital LS retrieved from institutional pathology files were evaluated.
Place and Duration of Study: The study has been performed in the Dermatology Clinic of the University of Catania, Italy, spanning a 19-year period.
Methodology: We previously demonstrated a high (17.4%) HPV detection rate in a study on 46 patients with genital LS. In this retrospective analysis we extended the analysis to a larger number of patients in order to strengthen these former data. HPV infection was assessed by polymerase chain reaction (PCR) in paraffin-embedded penile biopsies obtained from the glans or inner foreskin of 92 adult patients with penile LS and in brush cytology smears of penile healthy mucosa from an equal number of randomly selected control males matched for age. Statistical evaluation was performed using conditional logistic regression analysis. [4]
Role of Oncogenes and Tumor Suppressors in Metabolic Reprogramming and Cancer Therapeutics: A Review
Recently there has been a renewed interest on the signaling pathways and metabolic changes in cancer cells. It is well known that there are several oncogenes and tumor suppressors that affect cancer metabolism and re-engineer it for better growth and survival. The best description of tumor metabolism is the Warburg effect, which shifts from ATP production through oxidative phosphorylation to ATP production through glycolysis, even in the presence of oxygen. [5]
Reference
[1] Luo, J., Solimini, N.L. and Elledge, S.J., 2009. Principles of cancer therapy: oncogene and non-oncogene addiction. Cell, 136(5), pp.823-837.
[2] Park, M., Dean, M., Cooper, C.S., Schmidt, M., O’Brien, S.J., Blair, D.G. and Woude, G.F.V., 1986. Mechanism of met oncogene activation. Cell, 45(6), pp.895-904.
[3] He, L., Thomson, J.M., Hemann, M.T., Hernando-Monge, E., Mu, D., Goodson, S., Powers, S., Cordon-Cardo, C., Lowe, S.W., Hannon, G.J. and Hammond, S.M., 2005. A microRNA polycistron as a potential human oncogene. nature, 435(7043), pp.828-833.
[4] Rita Nasca, M., Lacarrubba, F., Paravizzini, G. and Micali, G. (2014) “Oncogenic Human Papillomavirus Detection in Penile Lichen Sclerosus: An Update”, International STD Research & Reviews, 2(1), pp. 29-37. doi: 10.9734/ISRR/2014/7983.
[5] Azharuddin, M. and Sharon, D. (2016) “Role of Oncogenes and Tumor Suppressors in Metabolic Reprogramming and Cancer Therapeutics: A Review”, Journal of Cancer and Tumor International, 4(4), pp. 1-27. doi: 10.9734/JCTI/2016/29641.
