Current Pharmaceutical Design - Volume 14, Issue 11, 2008

Intensive research to design chemotherapeutic therapies of cancer has been conducted for the last 70 years. Throughout the decades several groundbreaking observations have been made and countless compounds have been tested for their anti-neoplastic activities. Today we have arrived at a point where we understand in much greater detail the cell biology of tumor cells and are aiming at very specific cellular and Read More

Certain cancers may be auxotrophic for a particular amino acid, and amino acid deprivation is one method to treat these tumors. Arginine deprivation is a novel approach to target tumors which lack argininosuccinate synthetase (ASS) expression. ASS is a key enzyme which converts citrulline to arginine. Tumors which usually do not express ASS include melanoma, hepatocellular carcinoma, some mesotheliomas and Read More

Treatment options for metastatic renal cell carcinoma (RCC) have been limited due to its resistance to chemotherapy and radiotherapy. Benefits from immunotherapeutic agents provide only a small subset of patients. During the past decade major advances have been made toward understanding the molecular basis of RCC development. Such acquired knowledge has offered unique opportunities for the development Read More

For almost 5 decades later since it was first discovered in 1958, efforts continue to be made in the medicinal chemistry of camptothecin (CPT) and its derivatives. Thousands of CPT analogues have been prepared. However, many of the earlier CPT derivatives were either too toxic for clinical use or had very poor pharmacokinetics. Efforts in the last 2 decades were most successful and two derivatives, Irinotecan and topotecan, ha Read More

The progress made in cancer biology, genetics and biotechnology has led to a major transition in cancer drug design and development, from an emphasis on non-specific, cytotoxic agents to specific, molecular-targeted smart cancer drugs. Many of these targeted agents have shown to have improved selectivity for cancer versus normal cells and are associated with better anti-tumor efficacy and lower toxicity. The new gener Read More

Recent evidence from experimental and clinical studies links the development of intratumoral hypoxia and oxidative stress with malignant progression. Cellular adaptation induced by these environmental stresses is also associated with the emergence of drug resistant populations. This adaptation is most likely a multifactorial process involving coordination of various stress-induced signaling pathways, including those reg Read More

The objective of this review is to discuss the strategies adopted to improve the delivery of gemcitabine to tumors. Concomitant research in this area has implemented a wide variety of approaches such as, aerosolized formulations, prodrug conjugates, liposomes, nanoparticles and beads. Some of these strategies were also aimed at overcoming the rapid metabolization and drug resistance associated with gemcitabine. Aer Read More

Providing novel treatments to help cancer patients live longer and have better lives remains one of the biggest challenges of the pharmaceutical industry. Today much is known about the molecular and genetic causes of cancers thus facilitating the development of novel targeted cancer drugs with improved risk-benefit ratios compared to contemporary broadly-acting, cytotoxic cancer drugs. Antisense therapy, e.g. the use of s Read More

Tumor cells have an enhanced requirement for glucose, amino acids and DNA precursors. Since folates are required for the synthesis of thymidine and purines, the metabolism of folate has been exploited as an anti-cancer target for over 6 decades, with emphasis on the inhibition of DNA synthesis. However, folate is also used to generate methionine, which is essential for proliferation by virtue of its role in protein synthesi Read More