Tumor genetic alteration

Antibiotics form a large group of compounds of a vast structural diversity that are able to suppress or inhibit growth of one type of cells (microbial, fungal, tumor, genetically altered, etc.) and do not or to a lesser extent affect the growth of host cells. This definition is only very broad as it cannot embrace all the subtle effects of the various types of antibiotics. 

Though DNA damage-based therapies havebeen in use for many years, it has remained unclear why such treatment often causes the selective death of tumor cells while sparing adjacent normal tissue. The genetic alterations that occur in cancers that alter the DNA damage reponse may explain why such therapy can be efficacious. 

Fusenig, N. E., and P. Boukamp. 1998. Multiple stages and genetic alterations in immortalization, malignant transformation, and tumor progression of human skin keratinocytes. Mol Carcinog 23(3) 144—58. 

Several genetic alterations can influence radiosensitivity of cancer cells and radioresponsive tumors are known to allow more easily radiation-induced apoptosis. Therefore, the proper functioning of the apoptotic machinery regulates radiosensitivity. As described above, a cracial role is played by p53, and its downstream genes p21 and bax, in activating the apoptotic process. Those cancers with mutations at these levels are expected to be radioresistant. 

Recently, Caduff et al. (1999) have evaluated abnormalities in p53 and Ki-ra.v in malignant and borderline ovarian tumors of various histological types in paraffin-embedded tissues. The patterns of these genetic alterations in borderline and malignant neoplasms were compared and correlated with cell type and stage. This preliminary molecular analysis suggests that serous borderline tumors have the same molecular features usually associated with malignancy but are unlikely to represent a precursor of invasive serous carcinoma. On the other hand, mucinous borderline tumors may represent a precursor or variant of mucinous carcinoma of the ovary. 

Wei, M., Wanibuchi, H., Morimura, K. et al. (2002) Carcinogenicity of dimethylarsinic acid in male F344 rats and genetic alterations in induced urinary bladder tumors. Carcinogenesis, 23(8), 1387-97. 

Other promoters that may be useful for the design of targeted vectors are those induced by disease-specific conditions, such as hypoxia (see Table 1). Thus, a promoter responding to hypoxia through activation by the hypoxia-inducible factor-1 (HIF-1) has been successfully used for experimental cancer gene therapy [69], Disease-specific conditions in tumor cells can also directly result from genetic alterations or from altered signaling pathways. The latter are presumably... 

A great amount of evidence has demonstrated the relevance of the determination of genetic alterations of tumor cells and its impact on patient diagnosis,... 

Tumor promoters alter pathways that cooperate with the genetic changes present in the initiated cell to produce the selective growth of that cell. Generic mechanisms of tumor promotion are shown in Table 24.6. Although the precise molecular/bio-chemical mechanisms of tumor promotion are unknown, we do know that certain receptors, growth factors, transcription factors, cytokines, and kinases are involved in tumor promotion induced by a particular tumor promoter. 

---