oa Editorial [Hot topic: Recent Progress in Cancer Therapeutics (Guest Editor: Kurt S. Zaenker)]

In November 2008, the Chulabhorn Research Institute (CRI), Bangkok, Thailand, hosted an international conference on “Recent Progress in Cancer Therapeutics”. The conference was graciously presided over by Her Royal Highness Princess Chulabhorn, President of the CRI. Prof. Dr. Chulabhorn Mahidol opened the conference by delivering a keynote lecture on “Genetic Alterations in Nasopharyngeal Carcinoma in the Thai Population”. The conference was under the joined sponsorship of the American Association for Cancer Research (USA), the Chulabhorn Research Institute (Thailand), the Fritz-Bender-Foundation (Germany), the Network Complement Related Diseases (Switzerland) and KPMG (Germany), (Mrs. S. Bartels-Hetzler). The meeting report of this conference has been published recently [1]. PROGRESS IN CANCER THERAPEUTICS Low productivity and the escalating costs of drug development have been well documented over the past years. A fraction of new pre-clinical compounds successfully pass experimental test batteries, and less than 10% of these compounds that enter clinical trials ulitmately make it to the market [2]. Among different cancer therapy strategies, the chemotherapy could appear to be conceptually outclassed because of its low cancer cell selectivity in comparison with novel molecular mechanism based agents. However, combined strategies, to use the chemotherapeutic high killing potential with new molecule targeted agents, may become an effective anti-tumor treatment approach. The concept of the “magic bullet”, initially ascribed to immunoglobulins by Paul Ehrlich at the beginning of the 20th century and strengthened by the hybridoma technology of Kohler and Milstein in the mid 70s, can nowadays be attributed to different target-specific molecules. The declared paradigm is the development of “personalized and tailored drugs” that precisely target the specific molecular defects of a patient's tumor, if the molecular signature of the inidividual cancer cells can be deciphered. This is the most promising way in the development of improved cancer care for the third millennium. Crystal ball gazing is not the correct way, scientists are trained to study and analyse problems of interest and report critically their findings. So-called “scientific prophets” and “self-nominated experts” can be entertaining but at worst look egocentric and possibly ridiculous. Advances of cancer therapy have occured over the last decade in many fields. Recent developments in nanotechnology offer researchers opportunities to significantly transform cancer therapeutics by facilitating more efficient drug targeting and delivery [3]. The gene-directed enzyme prodrug therapy (GDEPT) has been evaluated for many years and is now entering late-stage clinical trials [4]. Angiogenesis has emerged as a valid therapeutic target and anti-VEGF therapies have clearly demonstrated anti-tumor efficacy in various malignancies, especially when combined with conventional cytotoxic chemotherapy [5]. The progress made in understanding of thermal biology, physics, and bioenigneering, coupled with advances in conventional chemo- and radiotherapy modalities have all contributed to the next generation of clinical thermal therapy [6]. Advances in radiobiology research in normal tissues in the last 50 years have had a major impact on radiation oncology. This includes the linearquadratic model to adjust doses in altered fractionation protocols, and quantitation of repopulation processes to avoid toxicities in accelerated regimen [7]. Increased aerobic glycolysis in cancer, known as Warburg effect, has been observed in various tumor cells. The current understanding of the Warburg effect provides exciting opportunities for the development of new drugs to preferentially kill cancer cells by targeting the glycolytic pathway [8,9]. The recent discoveries of epidemiological and molecular links between diabetes/metabolic syndrome and cancer originated from interdisciplinary-oriented research will give us special attention to the ways in which food and nutrition, physical activity, and body composition may modify treatment modalities [10]. Understanding the complexity of cancer depends on an elucidation of the underlying regulatory networks, at the cellular and intercellular levels and in their temporal dimension. Combined targeting of the Notch and the p53 and p63 pathways could improve the efficacy and reduce the toxicity of cancer therapies [11]. Although currently available data indicate that elimination of malignant cells often depends on classical apoptotic pathways (mitochondrial and/or death receptor pathways), the evidence is mounting that alternative apoptotic and non-apoptotic pathways may effectively contribute to tumor cell death. Interestingly, a growing number of reports recognize novel therapeutic targets, including proteins in control of endoplasmic reticulum and Golgi homeostasis [12]....