All pathways to cancer apoptosis meeting in Thiruvananthapuram (India)

Abstract

An extensive amount of research in the past three decades has revealed many pathways of cell death. Although ‘apoptosis’ is the term used for most types of cell death, the pathways that lead to it are not always the same. The list of agents that mediate apoptosis is constantly growing. Because cancer is a hyperproliferative disorder, apoptosis of cancer cells and not of normal cells is a critical issue. Both physiologic and pharmacologic inducers of apoptosis have been identified. At an international conference held in Kerala, India, scientists discussed how apoptosis occurs, what mediates it, what pharmacologic agents induce it, how it is genetically regulated, and its role in tumorigenesis and cancer. It is said that multiple pathways can lead to enlightenment. What better place to discuss this than Thirvananthapuram (Trivandrum), Kerala. Created by Parsuram, the legendary Brahmin ‘protector,’ Kerala, the southernmost state in India, sits where the Indian Ocean and Arabian Sea meet, where Vasco de Gama landed in search of spices, where St. Thomas landed in search of enlightenment, where the world’s second oldest mosque is located, and where one of the world’s oldest synagogues is located. The purpose of 31⁄2-day conference that convened on December 18, 2005 was to bring together laboratory and clinical scientists to share current knowledge and future strategies for promoting the death of cancer cells. The participants included over 450 physicians and researchers from 16 different countries worldwide. The format of the meeting was daily major symposia, parallel minisymposia, and poster sessions. Dr. Abdul Kalam, the President of India and an aerospace engineer, inaugurated the meeting and reminded the importance of stem cell cloning and nontoxic drugs in cancer treatment and the role of patient databases and genomics in cancer care. The conference began with a keynote speech delivered by Dr. John Mendelsohn (Houston, TX, USA). He enlightened the audience by describing the journey that led to the discovery of Erbitux, a monoclonal antibody against epidermal growth factor receptor (EGFR). Major highlight of Dr. Mendelsohn’s talk was that although this antibody induces apoptosis of EGFR-overexpressing tumor cells in the laboratory, its effect on tumor cells in patients was not mediated through EGFR but through antibody-dependent cell-mediated cytotoxicity. Erbitux when combined with chemotherapeutic agents is effective in some patients with colorectal cancer. Another interesting revelation was that this antibody induces antitumor response in patients that is unrelated to the level of EGFR expression in tumor cells. In a plenary lecture, Dr. Bharat Aggarwal (Houston, TX, USA), explained the connection between inflammation and cancer. A common molecule in these two processes is the tumor necrosis factor (TNF). He pointed out that natural products could serve as good drugs for treatment of both inflammation and cancer. One such product is curcumin, which exhibits a blocking effect on the TNF. Curcumin is being tested in early clinical trials in patients with multiple myeloma, breast cancer, and pancreatic cancer. Dr. S Krishna (Banglore, India) delineated the Notch oncogenic signaling pathway in human epithelial neoplasms. His group has identified deregulated Notch signaling in cervical cancer. The midmorning session began with a speech by Dr. Premkumar Reddy (Philadelphia, PA, USA), who discussed the human kinome. Eucaryotic and atypical protein kinases of the human kinome constitute more than 500 proteins mostly belonging to tyrosine kinases or serine/threonine kinases. Many of these kinases are either mutated, constitutively active, or overexpressed in human cancers. The best example of such an agent is imatinib, the inhibitor of Bcr-Abl tyrosine kinase, he pointed out. Dr. Raj Puri (Bethesda, MD, USA) discussed early laboratory, preclinical, and animal model studies that were conducted with an immunotoxin composed of IL-13 and a mutated form of Pseudomonas exotoxin. These preclinical results were translated into phase I/II investigations in patients with solid tumors. Dr. Kapil Mehta (Houston, TX, USA) discussed the implications of elevated tissue transglutaminase expression in the development of drug resistance and metastatic phenotypes in tumor cells. Cell Death and Differentiation (2006), 1–2 & 2006 Nature Publishing Group All rights reserved 1350-9047/06 $30.00