Resistance to anticancer agents

Earlier, N-alkylated 1,4-DHPs of general formula (57) (58) were synthesized that were found to possess a remarkable activity for overcoming resistance to anticancer agents. The DHPs were used in combination with anticancer agents. The DHPs were also found very potent in enhancing the therapeutic activity of anticancer agents [103]. 

Brockman, R.W. (1963) Mechanisms of resistance to anticancer agents. Advances in Cancer Research, 57, 129-234. 

As any potential therapeutic agents, the biological effect of G-quadruplex ligands may be overcome by the appearance of acquired-resistance phenotypes or to be lowered by the intrinsic expression of proteins already known to be associated with resistance to anticancer agents. The selection as well as the analysis of resistant cells is a well-known strategy to obtain information on the mechanisms of drug inactivation and on their target proteins, if a modification of their expression, or a mutation can be related to the resistance phenotype. 

Altretamine, formerly known as hexamethylmelamine, is similar in structure to alkylating agents but is known to have anticancer activity in cancer cells resistant to alkylating agents. Altretamine is well absorbed after oral administration and undergoes rapid and extensive demethylation in the liver. Peak plasma concentrations were observed 0.5 to 3 hours after administration. The terminal half-life is 4.7 to 10.2 hours. 

DRUG RESISTANCE Membrane transporters play critical roles in the development of resistance to anticancer drugs, antiviral agents, and anticonvulsants. P-glycoprotein, which exports many chemotherapeutics from cells, is overexpressed in tumor cells after exposure to cytotoxic anticancer agents. Other transporters (e.g., breast cancer resistance protein [BCRP], organic anion transporters, and several nucleoside transporters) also have been implicated in resistance to anticancer drugs. 

Kerbel RS. Inhibition of tumour angiogenesis as a strategy to circumvent acquired resistance to anticancer therapeutic agents. Bioessays 1991 13 31-36. 

Brown JM, Wilson G (2003) Apoptosis genes and resistance to cancer therapy What does the experimental and clinical data tell us Cancer Biol Ther 2(5) 477-490 Brown JM, Wouters BG (1999) Apoptosis, p53, and tumor cell sensitivity to anticancer agents. Cancer Res 59(7) 1391-1399... 

The overexpression of the anti-apoptotic protein Bcl-2 in cancer has been associated with resistance to chemotherapeutic agents. The phosphorylation of Bcl-2 is one mechanism by which antimicrotubule agents in clinic such as paclitaxel, taxotere and vinblastine inactivate the Bcl-2 proteins. Many natural products and semi-synthetic molecules are used in clinic for anticancer activity. In this chapter, the importance of the Bcl-2 phosphoiylating molecule from nutraceuticals that shed light on the future development of molecules for chemoprevention and anticancer drugs will be discussed. The roots of Licorice (Glycyrrhiza glabra) have been used in traditional medicine for a variety of... 

Breast cancer resistance protein (BCRP) is another ATP-dependent efflux transporter that confers resistance to a variety of anticancer agents, including... 

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