In 1920s, Otto Warburg described the phenomenon of 'aerobic glycolysis', the ability of tumour cells to convert glucose to lactate in the presence of normal oxygen conditions. Warburg's hypothesis of an altered metabolism in cancer cells found no immediate acceptance, though it was latter confirmed for most human tumours. With the advent of molecular biology the focus in tumour research has shifted towards the search for oncogenes. However, the interest in cancer molecular profiling eventually led to a renaissance of the Warburg effect trying to combine genetic alterations with effects on metabolism with the help of modern analytic technologies to rapidly analyze broad varieties of metabolites in various tissues and bodyfluids (metabonomics).
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In: Fox , BA , Schendel , D J , Butterfield , L H , Aamdal , S , Allison , J P , Ascierto , P A , Atkins , M B , Bartunkova , J , Bergmann , L , Berinstein , N , Bonorino , C C , Borden , E , Bramson , J L , Britten , C M , Cao , X , Carson , W E , Chang , A E , Characiejus , D , Choudhury , A R , Coukos , G , de Gruijl , T D , Dillman , R O , Dolstra , H , Dranoff , G , Durrant , L G , Finke , J H , Galon , J , Gollob , J A , Gouttefangeas , C , Grizzi , F , Guida , M , Hakansson , L , Hege , K , Herberman , R B , Hodi , F S , Hoos , A , Huber , C , Hwu , P , Imai , K , Jaffee , E M , Janetzki , S , June , C H , Kalinski , P , Kaufmann , H L , Kawakami , K , Kawakami , Y , Keilholtz , U , Khleif , S N , Kiessling , R , Kotlan , B , Kroemer , G , Lapointe , R , Levitsky , H I , Lotze , M T , Di Maio , M , Marschner , J P , Mastrangelo , M J , Masucci , G , Melero , I , Nelief , C , Murphy , W J , Nelson , B , Nicolini , A , Nishimura , M I , Odunsi , K , Ohashi , P S , O'Donnell-Tormey , J , Old , L J , Ottensmeier , C , Papamichail , M , Parmiani , G , Pawelec , G , Proietti , E , Qin , S , Rees , R , Ribas , A , Ridolfi , R , Ritter , G , Rivoltini , L , Romero , P J , Salem , M L , Scheper , R J , Seliger , B , Sharma , P , Shiku , H , Singh-Jasuja , H , Song , W , Straten , P T , Tahara , H , Tian , Z , van der Burg , S H , von Hoegen , P , Wang , E , Welters , M J , Winter , H , Withington , T , Wolchok , J D , Xiao , W , Zitvogel , L , Zwierzina , H , Marincola , F M , Gajewski , T F , Wigginton , J M & Disis , M L A 2011 , ' Defining the Critical Hurdles in Cancer Immunotherapy ' , Journal of Translational Medicine , vol. 9 , no. 1 , 214 . https://doi.org/10.1186/1479-5876-9-214
ABSTRACT: Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators, others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet be overcome to improve outcomes of patients with cancer.