Translational research in oncology

The purpose of translational oncology research is to build a bridge that allows the fastest possible transfer of new information and discoveries from the laboratory to therapy and clinical management to generate those innovative therapies which are required to address the most urgent clinical problems in the field.

The translational and molecular medicine approach is currently growing in the international arena, as demonstrated by the increasing number of scientific journals, meetings, educational and training activities dealing with this issue, and the establishment of new centres for translational research, especially in the oncology field. Locally, the most important international challenge that we are facing now is to set up the most efficient transfer system capable to bring the innovative knowledge to the market at national level to increase and maintain the competitiveness of our country in this field.
In particular, with regard to the field of oncology, the goal of translational research is the transformation of scientific discoveries from the laboratory into clinical applications to reduce cancer incidence and specific mortality. This research approach is well rendered by the English phrase “from the bench to the bedside”. For many reasons, and often because of too many regulations, diagnostic and therapeutic implementations are delayed for many years after the experimentation was actually carried out in the laboratory. Researchers working in the most advanced oncology laboratories who know about basic research and clinical needs may speed up the application of this knowledge to the clinical practice. Therefore, the “Translational Oncology” research will merge the necessary expertises and skills to promote design and implementation of multidisciplinary research projects with particular regard to the development of new therapeutic approaches for cancer. It will also carry on basic, applied and industrial research in the context of cancer biology to expand our knowledge on the molecular mechanisms of transformation and clinical progression.

Several INBB researchers have already significantly contributed to this field of research showing high competitiveness in the international arena. In particular, the work of the Research Unit (RU) of Parma has already opened the way to the development of new therapeutic approaches, such as the use of natural substances for chemo-prevention of Prostate Cancer (PCa) in patients. The expertise includes identification of active substances, development of biomarkers for monitoring therapeutic response, assessment of the clinical efficacy of chemo-prevention, study of cancer progression and resistance to therapy.
PCa is the second most common male cancer in western Countries, but it will soon become the first, due to the ageing of the population. The specific mortality for PCa is only 15% because only the aggressive, metastatic form kills the patient. The vast majority of diagnosed PCa is actually indolent. Because PCa is a very elusive disease, the scientific information available at the moment do not allow to discriminate indolent from aggressive disease. The current scenario in the clinical management of these patients is therefore characterized by “over-diagnosis” and “over-treatment” of indolent PCa, and lack of efficacy of treatments for aggressive PCa. Therefore, the most important goal in this field is a better clinical management of all urological patients and PCa in particular. In 2008, 382,000 new cases of PCa have been estimated only in Europe. The above mentioned INBB RU has already identified and clinically validated a “gene signature” with diagnostic and prognostic power for PCa able to diagnose and discriminate the aggressive disease. The same signature has the potential power to correctly detect individual response to treatment. In addition, a chemo-preventive therapeutic strategy has been already developed, leading to a phase II clinical trial which led to a decrease in PCa diagnosis by 90% in high-risk subjects in absence of significant side effects. A key cancer suppressor gene (CLU) has been identified, and proposed as probably the best therapeutic target for an anti-metastatic therapy against PCa.
The strong commitment of INBB researchers in this specific area is well described in the activity reports submitted at INBB National Conferences. It is worth to mention here the most recent ones, at the IX INBB National Conference held in Rome on 21-22 October 2010, and the X INBB National Conference held in Rome on 22-23 October 2012. Detailed programs and abstracts of the scientific reports are available on the website: www.inbb.it

In the near future, the ability to implement these results already obtained by means of further clinical validation studies will be crucial for implementation and quick transfer to clinical practice. This activity, which will maximize the benefit for the patient, will make use of many collaborations, already active, with pharmaceutical and biomedical industries. INBB will gather the best experts to face the most challenging targets on PCa by focusing on the identification of a rational method to discriminate aggressive from indolent disease, the developing of a less expensive and more conservative treatment for indolent disease, the implementation of a better clinical management of lower-risk or indolent patients, with significant savings and immediate benefits for the local health System. If successful, this strategy will allow to redirect more resources on aggressive disease, with the aim to identifying new molecular targets and new therapies of the metastatic form.

Modena, Milano, Parma and Torino are among the several INBB RUs already operating within the “Translational Oncology” frame.

SOME RECENT PUBLICATIONS

• Rizzi F, Naponelli V, Silva A, Modernelli A, Ramazzina I, Bonacini M, Tardito S, Gatti R,Uggeri J, Bettuzzi S. Polyphenon E(R), a standardized green tea extract, induces endoplasmic reticulum stress, leading to death of immortalized PNT1a cells by anoikis and tumorigenic PC3 by necroptosis. Carcinogenesis. 2014 Jan 20. [Epub ahead of print]
• Panico F, Casali C, Rossi G, Rizzi F, Morandi U, Bettuzzi S, Davalli P, Corbetta L, Storelli ES, Corti A, Fabbri LM, Astancolle S, Luppi F. Prognostic role of clusterin in resected adenocarcinomas of the lung. Lung Cancer. 2013 Mar;79(3):294-9.
• Davalli P, Rizzi F, Caporali A, Pellacani D, Davoli S, Bettuzzi S, Brausi M, D’Arca D. Anticancer activity of green tea polyphenols in prostate gland. Oxid Med Cell Longev. 2012;2012:984219.
• Davalli P, Rizzi F, Caldara GF, Davoli S, Corti A, Silva A, Astancolle S, Vitale M, Bettuzzi S, Arcari M, Azzali G. Chronic administration of green tea extract to TRAMP mice induces the collapse of Golgi apparatus in prostate secretory cells and results in alterations of protein post-translational processing. Int J Oncol. 2011 Dec;39(6):1521-7.
• Hassan MK, Watari H, Christenson L, Bettuzzi S, Sakuragi N.Intracellular clusterin negatively regulates ovarian chemoresistance: compromised expression sensitizes ovarian cancer cells to paclitaxel. Tumour Biol. 2011 Oct;32(5):1031-47.
• Bhutia SK, Das SK, Kegelman TP, Azab B, Dash R, Su ZZ, Wang XY, Rizzi F, Bettuzzi S, Lee SG, Dent P, Grant S, Curiel DT, Sarkar D, Fisher PB. Mda-7/IL-24 differentially regulates soluble and nuclear clusterin in prostate cancer. J Cell Physiol. 2012 May;227(5):1805-13.
• Moretti RM, Mai S, Montagnani Marelli M, Rizzi F, Bettuzzi S, Limonta P. Molecular mechanisms of the antimetastatic activity of nuclear clusterin in prostate cancer cells. Int J Oncol. 2011 Jul;39(1):225-34.