Combinatorial chemistry in cancer research

Abstract  Among the different strategies to treat cancer, chemotherapy approaches are the subject of intense research efforts. There is still a high demand for new anticancer drugs exhibiting improved efficiency and selectivity for their use in combined therapy strategies. The high development of molecular and cellular biology tools has made possible the set up of simple in vitro assays, susceptible to automation, thus bringing about the possibility of rapid screening of hundreds of compounds. Chemistry has reacted to this challenge by developing a new technology: combinatorial chemistry. By this procedure large collections of compounds, known as chemical libraries, can be prepared in a rapid and efficient manner. In recent years, combinatorial chemistry has had a great impact on drug discovery programmes addressed to tackling cancer pharmaceutical targets. In this review, the contribution of this technology to the discovery of anticancer drugs that are currently in clinical trials or already in the market is discussed.

Aggressive surgical treatment for T4 gastric cancer

Abstract  Surgical treatment for locally advanced gastric cancer remains controversial, and many still question the benefits of extended resection. The aim of this study was to evaluate the effectiveness of combined resection of the involved organs with regard to survival in patients with gastric cancer. Between 1993 and 2000, among the 1638 patients with gastric cancer who underwent gastrectomy, 82 were found to have evidence of adjacent organ spread at laparotomy. A retrospective analysis of these patients was performed. Curative resections were carried out in 50 patients, whereas noncurative resections were performed in 32 patients. The 5-year survival rate in the group undergoing curative resection was 36.9%. The survival rate in the R0 group was significantly higher than the survival rate for patients undergoing noncurative resections. There was no significant difference in survival rates between patients with pT3 cancer and those with pT4 cancer. Seventy-one patients were pathologically proved to have lymph node metastasis, and the survival rate for patients with a lymph node ratio greater than 0.2 was lower than that in other groups. In multivariate analysis, peritoneal dissemination, lymph node ratio, and histologic findings were the predictors of survival. Patients with T4 gastric carcinoma, even with lymph node metastasis, might have benefited from aggressive surgery with curative intent.

Changes in Cancer-Related Risk Perception and Smoking Across Time in Newly-Diagnosed Cancer Patients

We examine the bidirectional relationships between cancer risk perceptions and smoking behavior among newly diagnosed cancer patients (N=188) during hospitalization for surgical resection, and at three and 12 months subsequently. Those with higher perceptions of risk for developing another cancer at three months were most likely to abstain from smoking by twelve months. Patients were relatively accurate in their cancer risk perceptions, with relapsers and continuous smokers reporting higher levels of risk perceptions at twelve months. Finally, those who quit smoking by 12 months felt at lower risk for developing cancer by 12 months. None of these relationships were significant between baseline and three months. Results indicate that perceived risk of cancer recurrence may be clinically useful in motivating smoking cessation after the acute cancer treatment phase is over. This study justifies an expanded theoretical framework attending to the distinct, prospective influences of illness risk perceptions on health behavior, and of health behavior on illness risk perceptions.

Advances in surgical technique for primary rectal cancer

Abstract  Rectal cancer continues to produce significant morbidity and mortality, with about 41,000 new cases diagnosed per year in the United States. Recent advances in the management of rectal cancer, including the standardization of total mesorectal excision and the increasing application of neoadjuvant chemoradiation, have led to an increase in patients undergoing sphincter preservation and a decrease in the rate of local-regional tumor recurrence. This article reviews the current literature that affects the surgeon’s decisions regarding preoperative staging and operative management of the patient diagnosed with rectal cancer.

EGFR-Targeted Therapies in Colorectal Cancer

The management of colorectal cancer relies heavily on the combination of the pyrimidine analog antimetabolite 5-fluorouracil with the platinum-based drug oxaliplatin or the topoisomerase inhibitor irinotecan. Optimization of dosing and scheduling of these agents to improve response and survival continues to evolve. Meanwhile, the rational targeting of molecular signaling pathways that are involved in the etiology of malignancies is currently one of the most promising strategies in novel anticancer drug development. New classes of drugs that target the epidermal growth factor receptor are among the most clinically advanced molecular-targeted therapies and have shown efficacy in colorectal cancer. The current status of epidermal growth factor receptor-targeted therapeutic agents is reviewed, with emphasis on their role in the management of colorectal cancer.

Advances in cancer pain management

Abstract  Control of malignant pain and related symptoms is paramount to clinical success in caring for cancer patients. To achieve the best quality of life for patients and families, oncologists and palliative care clinicians must work together to understand problems related to psychologic, social, and spiritual pain. Pain is the primary problem targeted for control using the World Health Organization’s (WHO) analgesic ladder. This article focuses on increased knowledge of analgesic action that may enable expansion of the WHO analgesic ladder to fulfill the broader objectives of palliative medicine. We discuss clinical experience with several classes of drugs that are currently used to treat cancer pain: 1) nonsteroidal anti-inflammatory drugs (NSAIDs), with emphasis on cyclooxygenase-2 (COX-2) inhibitors; 2) opioid analgesics, with specific emphasis on methadone and its newly recognized value in cancer pain; 3) ketamine, an antagonist at N-methyl D-aspartate (NMDA) receptors; and 4) bisphosphonates, used for pain resulting from bone metastases. New concepts that compare molecular actions of morphine at excitatory opioid receptors, and methadone at non-opioid receptor systems, are presented to underscore the importance of balancing central nervous system excitatory (anti-analgesic) versus inhibitory (analgesic) influences.

Yeast and Cancer

The discovery of genes that control cell division in yeast, and their relation to cancer, is reviewed.