Italian-American Foundation Honors Antonio Giordano, MD, PhD Founder & President of Sbarro Health Research Organization

Newswise — Italian-American Foundation, Filitalia, honors Antonio Giordano, MD, PhD, Founder & President of Sbarro Health Research Organization at Temple University with the Humanitarian award at the foundation’s 31st Anniversary Gala.

Filitalia International & Foundation celebrates 31 years of commitment, dedication and service at their Annual Gala Dinner on Sunday, November 11, 2018. The foundation and its donors have contributed to initiatives championed by the Italian American community in the Greater Philadelphia area, among them the opening of the History of Italian Immigration Museum in 2014.

”The mission of this foundation is to help promote the talent of Italian-Americans in various industries and disciplines,” Giordano says, “ and considering that historically, Italy has generated great discoveries in the arts, medicine, and business, it is vital for us to carry on that tradition and maintain that legacy in the modern world.”

“To be recognized as an example of the contribution of Italian-Americans in this country, by a foundation that was created by other professional, successful Italians, is a great honor,” says Giordano.

In 1993, Antonio Giordano, M.D., Ph.D., founded the Sbarro Institute with a generous donation from Mario Sbarro, the Founder of the Sbarro restaurant chain, following Dr. Giordano’s discovery of the tumor suppressor gene pRb2. Giordano now serves as Director of the Sbarro Institute for Cancer Research and Molecular Medicine and Center of Biotechnology, at the College of Science and Technology, Temple University, as well as Professor of Pathology at the University of Siena, Italy.

Giordano recently organized the medical conference, “The Impact of Environment and Healthy Lifestyles in Human Health,” at the National Italian American Foundation (NIAF) annual convention, with awards for achievement in medicine presented from the Giovan Giacomo Giordano Foundation.

The research team lead by Giordano continues to make significant medical breakthroughs, including recent studies on the identification of a potential target for treatment of mesothelioma, understanding a protein that governs cell death in cancer, and further potential of the CDK9 gene to control the cell cycle.

The Filitalia International & Foundation celebrates their 31st anniversary with other honorees including Lee Norelli, AP Construction – President, UNICO National, and Dr. Louis De Angelo, Superintendent of Schools for the Diocese of Wilmington, DE.

About Filitalia International & Foundation

Filitalia International is a non profit organization, founded in 1987 to promote and preserve the Italian tradition, language and culture worldwide. The goal is to consolidate and expand the Italian heritage through social events and humanitarian programs. Filitalia is committed in several projects, such as scholarships, Italian language classes, networking for young professionals and cultural events, by encouraging anyone to learn more about Italy and its heritage.

The Filitalia Foundation 501 (c) 3 opened the History of Italian Immigration Museum with the aim to sustain Italian-American heritage through stories that resonate with diverse cultures, connecting the Italian-American community with its cultural roots, and sharing Italian heritage with people of all backgrounds.

The organization was founded by cardiologist Dr. Pasquale Nestico, inspired by a love for his birthplace, Isca sullo Ionio, in Calabria, Italy. Nestico is joined in leading the foundation by past president Rosetta Miriello, and incoming president Marc Virga.

BOARD OF DIRECTORS

President Marc Virga

Founder Pasquale F. Nestico, M.D.

Immediate Past President Rosetta Miriello

1st Vice President Paula DeSantics-Bonavitacola

2nd Vice & Governor Henry Amanto

Secretary Alexis Tulio

Treasurer Gianfranco Buonamici

Legal Counsel Joseph Rollo, Esq.

Auditor Ernest DiFilippo

Board Members

Anthony Colavita, MD – Joseph D’Ascenzo, Esq.

Anna Di Paola – Anna Di Nardo

Saverio Nestico – Giacomo Presta

Mario Presta – Salvatore Rosati – Nicholas Santangelo

Executive Director

Marco Circelli

About the Sbarro Health Research Organization

The Sbarro Health Research Organization (SHRO) is non-profit charity committed to funding excellence in basic genetic research to cure and diagnose cancer, cardiovascular diseases, diabetes and other chronic illnesses and to foster the training of young doctors in a spirit of professionalism and humanism. To learn more about the SHRO please visit www.shro.org

 

Original Newswise Release

Healthier Planet, Healthier People, and More Innovative Medical Science with Italian-American Researchers at Annual NIAF Convention

Brochure  The Sbarro Health Research Organization (SHRO), in collaboration with Temple University’s College of Science and Technology, the National Italian American Foundation (NIAF), and the Giovan Giacomo Giordano Foundation will host the medical conference “The Impact of Environment and Healthy Lifestyles in Human Health” 9 A.M on Saturday, October 13th at the Marriot Wardman Park Hotel in Washington, D.C.

The conference will feature introductions presented by SHRO’s President Antonio Giordano who is also director of Temple’s Sbarro Institute for Cancer Research and Molecular Medicine and Center for Biotechnology and by Temple University Vice President for Research, Michele Masucci, PhD. Temple and CST are leaders in biotech research and development, and recently launched masters programs in both bioinnovation and biotechnology.

Guest speakers include Roberto Lucchini, MD, Giuseppe Loianno, PhD., and Giacomina Massaro-Giordano, M.D. Dr. Lucchini,  Director of the Occupational Medicine Center of the Ichan School of Medicine at Mount Sinai NY and  professor at University of Brescia Italy, will address “Impacts of Environmental Hazards on Human Health: From the 9/11 Dust to the Industrial Emissions of Taranto, Puglia”. Dr. Loianno will discuss “Drones for Health: Agricultural and Infrastructure Monitoring” and Dr. Massaro-Giordano will report on “Dompe: FDA Approval of the First Medicine Based on Human Nerve Growth Factor: An Italian Pharma Success Story.”  A special recognition will be given to Nathalie Dompé for her work and effort promoting social responsibility and in particular with the visually impaired.

The conference will culminate in the presentation of the 2018 Giovan Giacomo Giordano NIAF Lifetime Achievement Award for Ethics and Creativity in Medical Research by  Dr. Giacomina Massaro. This award was established seven years ago in honor of Dr. Giordano’s father, the late Professor Giovan Giacomo Giordano, renowned pathologist and former chair of the Department of Pathology, Second University of Naples, who dedicated more than sixty years of his life to the study of cancer and the role of environmental factors in the onset of this disease.  Professor Giovan Giacomo Giordano was also a major advocate against corruption in the Italian medical community and driving force for the establishment of medical ethical standards among his colleagues. Furthermore, special guest, Ms. Nathalie Dompé, CEO Dompé Holdings, Vice President, Business Development at Dompé Pharmaceuticals responsible for the oversight, market development and strategic approval of all new programs launched by the Company in the United States, will receive the Special Award for Societal Impact in Business & Biotechnology.

About the Sbarro Health Research Organization

The Sbarro Health Research Organization (SHRO) is non-profit charity committed to funding excellence in basic genetic research to cure and diagnose cancer, cardiovascular diseases, diabetes and other chronic illnesses and to foster the training of young doctors in a spirit of professionalism and humanism. To learn more about the SHRO please visit www.shro.org

New MicroRNA Target May Inhibit Mesothelioma and Unveils Method to Identify Potential Treatments

Newswise — Inhibition of miR-24-3p reduced growth of cancer cells and was found to regulate proteins as a potential treatment target for Mesothelioma (MPM). The new potential target, and the method researchers have used to identify it, is an important step in addressing this challenging disease.

MPM is a lethal cancer with increasing worldwide incidence and resistance to treatment. Despite this dreadful scenario, preclinical research has struggled to identify potential treatments.

“The ‘one more indication’ strategy is not the right approach for Mesothelioma,” say Professors Antonio Giordano and Luciano Mutti from the Sbarro Institute for Cancer Research and Molecular Medicine at Temple University and the Italian Group for Mesothelioma (GIMe), referencing attempts to discover existing drug combinations that may yield an effective treatment. “Drugs with some activities in other tumours have utterly failed in MPM,” they say, “providing evidence we have to rethink what we have been doing so far and start over from a solid biological background.”

Researchers published their findings this month in Cancer Research, in the study titled A polysome-based microRNA screen identifies miR-24-3p as a novel pro-migratory miRNA in mesothelioma.

MicroRNAs (miRNAs) are small, non-coding RNA molecules, which target genes and regulate gene expression and function. Abnormal expression of miRNA plays a relevant role in cancer biology and they are therefore a potential target for the development of innovative cures.

“We have identified a novel approach for identifying relevant miRNA in cancer biology,” Professor Biffo of the National Institute of Molecular Genetics in Milan explains. “By examining the polyribosomes where translation occurs, this ‘focused’ search has allowed us to identify that miR-24-3p (a particular miRna) expression is relevant to cancer progression and metastasis.”

Biffo, in collaboration with the Sbarro Institute for Cancer Research and Molecular Medicine at Temple University, University of Siena, Columbus University, Leicester University, and supported by GIMe, has conducted a research program that has made significant steps forward in the fight against MPM.

“The first take home message for us is, ‘hunt where the ducks are,’” the authors say. “High levels of miR24-3p are detected only where they exert their biological effects (the polyribosomes), and increase tumour cell migration and Mesotheliomia progression via an enzyme family called Rho Kinase. These enzymes can be inhibited by specific drugs. Now it is time to translate our research into a pharmaceutical solution to develop this potential therapy,” the authors conclude.

Original Newswise Release

Olive Oil Production Threatened by New Deadly Plant Pathogen Recently Introduced to Europe

One of the iconic ingredients of the Mediterranean diet, which often has been associated with beneficial effects in the prevention of cancer as well as several other disorders, is extra-virgin olive oil. For thousands of years, olive trees were planted on Mediterranean coasts, initially by ancient Greek colonists, followed by several other civilizations and cultures, one generation after the other. This enduring agricultural practice led to the formation of the so-called “olive tree forest,” a monument to the Mediterranean environmental and cultural heritage containing millennial trees, found particularly in Southern Italy, in the Apulia region. Olive oil production from this region propelled and sustained olive oil consumption; however, this production is now endangered by a new, deadly plant pathogen, which arrived in Europe a few years ago.

“The olive orchards in Southern Italy are facing an ominous threat,” says Temple’s adjunct professor Enrico Bucci, PhD, Director of the Cancer Systems Biology & eHealth Programs of the Sbarro Institute for Cancer Research and Molecular Medicine at Temple University. Earlier in 2017, under appointment by the revered Accademia dei Lincei (one of the oldest and most prestigious scientific academies in the world), Bucci applied his skills in the fields of data mining and analytics, which he usually deploys in the field of Systems Biology, to extract and process data on thousands of Apulian olive trees, which led him to confirm the correlation between the bacterium and the disease. After that, he revised hundreds of scientific papers, detailing the ecology, the pathogenic potential, the molecular biology and all other relevant aspects of the interactions between the bacterium, its vectors and the host plants, publishing a new, state-of-art review, which got the cover of the Elsevier journal “Biochemical and Biophysical Research Communications.”

Fig. 3 from original research article: Some molecular details of the X. fastidiosa life cycle. rpfF, fimA, hxfA, hxfB, chiA, phoP/phoQ, PD1671 are all bacterial genes differentially expressed at various stages. DSF stands for “diffusible signalling factor”. See full text article for further details.

“The culprit of the epidemic, which is killing millennial olive trees and devastating the Apulian agricultural landscape, is the bacterium Xylella fastidiosa. Its pauca subspecies, which is colonizing Italy, is able to rapidly kill the olive trees, at odds with all the subspecies established in California, which mainly threaten vineyards and almonds,” says Bucci

There is no established cure for the infection; however, containment policies applied in California to prevent further spreading of the epidemic of Xylella in vineyards seem to work, suggesting that similar policies should also be enforced in Italy – after taking into accounts the obvious differences between olives and grapevines.

“As I learned by studying the available scientific literature, researchers from all over the world are working hard to find solutions, and there are indeed some promising approaches under study, aiming e.g. at blocking the infection or finding resistant olive cultivars – however, scientists need more time to accumulate stronger evidence. That’s why containing the infection in Southern Italy by all available means is crucial,” says Bucci, in line with the prevalent opinion in the scientific community.

“I hope that my article, by providing a revision of all the best available scientific evidence, will inspire politicians and local authorities to follow the scientific consensus, instead of the opinions of non-expert influencers or isolated, controversial hypotheses which lack solid scientific ground,” concludes Bucci.

Original Elsevier News Posting                      ScienceDirect Article        PubMed Abstract

Understanding Cancer Heterogeneity Could Further Reduce Chemo Use, Says Expert

Credit: Antonio Giordano

“Understanding cancer heterogeneity could further reduce chemo use,” says cancer research expert Antonio Giordano, MD, PhD, Director of the Sbarro Institute for Cancer Research and Molecular Medicine at Temple University. “Further study of cases that can successfully be treated with hormone- and immunotherapy, and how to identify them, will unlock this potential.”

Giordano refers to the TAILORx study, published by The New England Journal of Medicine this week, which describes treatment outcomes in breast cancer comparing cases receiving both endocrine therapy and chemotherapy, versus those receiving only endocrine therapy. Under certain conditions, including the early-stage development of tumor size, and the tumor not having spread to any peripheral lymph nodes, endocrine therapy alone resulted in nearly identical rates of survival and recurrence as endocrine- and chemotherapy combined.

“It is important to underscore that this specific study refers to patients with small tumors and no lymph node infiltrations,” says Giordano. “Women with early-stage breast cancer may be able to avoid chemotherapy, which is exciting, because there are pros and cons associated with it. The treatments have unavoidable effects on healthy cells as well as cancer cells”

“The goal of precision medicine moving forward,” Giordano says, “is to identify more sophisticated approaches to this problem of cancer heterogeneity. Every type of cancer, at the molecular level, can have a cell environment that changes and evolves through the course of the disease. Or from patient to patient.”

“Only by understanding specific targets or molecules responsible for key cellular processes will we be able to understand, with precision, new options of therapeutic target that could replace chemotherapy altogether,” Giordano says.

“The precision target is not yet precise enough,” Giordano says. “But the option to spare many patients the potential harmful effects of chemo is a sign we are moving in the right direction.”

Antonio Giordano, MD, PhD, Director of the Sbarro Institute for Cancer Research and Molecular Medicine and Center of Biotechnology, College of Science and Technology, Temple University and Professor of Pathology at the University of Siena, Italy.

In 1993, Antonio Giordano, M.D., Ph.D., founded the Sbarro Institute with a generous donation from Mario Sbarro, the Founder of the Sbarro restaurant chain, following Dr. Giordano’s discovery of the tumor suppressor gene pRb2.

About Sbarro Health Research Organization

Sbarro Health Research Organization conducts research in cancer, diabetes, and cardiovascular disease. Based in Philadelphia, Pennsylvania on the campus of Temple University, our programs train young scientists from around the globe.

Original Newswise Posting                         PubMed Abstract

In Debate of Scheduled Versus Spontaneous Exercise, Which Motivates You More?

Older adults seem to be more motivated by scheduled workouts, including the role of a fitness coach or a significant person involved in their exercise goals, when compared to those getting exercise only through spontaneous physical activity.

Researchers tested a mathematical and psychological model on two different samples of older adults: the first doing spontaneous physical activity, the second engaged in an exercise class. This theoretical model tried to understand what is really important to  encourage and maintain the intention to do physical activity.

The results suggest a psychological construct called autonomous motivation, in which subjects experience a sensation of value and self-worth tied to the activities. Participants that felt a sense of autonomous motivation during an exercise program were more successful at beginning and maintaining a more healthy, active lifestyle, despite possible interruptions caused by physical discomfort or scheduling challenges.

The researchers published their findings in the journal Gerotarget, a section of Oncotarget. Psychologists from the faculty of Medicine and Psychology of Sapienza, University of Rome, led by Prof. Fabio Lucidi, partnered with the American research team of Prof. Antonio Giordano, Director of the Sbarro Institute for Cancer Research and Molecular Medicine, Department of Biology, Temple University, and University of Siena, Italy to produce the study.

The aging of the world’s population is a steadily growing phenomenon, with the older adult population expected to triple by the year 2050. Therefore, taking care of older adults is considered an important social goal. Physical activity and exercise are two behaviors that may prevent diseases, cognitive decline, and loneliness among older adults. Despite the well-established positive effects of physical activity and exercise, data shows that few older adults are engaged in these behaviors.

“This study,” explains first author Federica Galli, “shows clearly that the sensation autonomous motivation leads older adults to be successful implementing these healthy behaviors.”

“Thanks to the new therapies produced by oncological research, a lot of patients with oncological diseases will be able to live normal life expectancies,” Giordano adds. “For this reason, it’s very important to study the mechanisms to motivate people to exercise, given the therapeutic role of fitness and physical activity in oncological diseases.”

The study provides guidelines for professionals that work in preventive medicine in the older population, so that they can support the perception of autonomy that could increase their motivation to start and maintain physical activity and exercise.

“The NCI of Naples has always been sensitive to this issue,” says Scientific Director of the National Cancer Institute of Naples, Gerardo Botti. “In the future, I am already  considering the implementation of new studies that would consider the application of this model to target populations more at risk such as our oncology patients,” Botti says.

 

Original Newswise Posting

Molecular Inhibitors Can Boost Natural Tumor Suppression to Fight Lung Cancer and Mesothelioma

Inhibition of the oncogenic kinase AKT, a key protein governing the cell cycle, was found to arrest cancer cell proliferation and triggered their programmed death by apoptosis. The study, published today in Oncogene, represents significant progress in the clinical translation of previous basic scientific discoveries.

“Understanding the molecular features that govern cancer cell behavior is the basis for the design of the so-called ‘targeted therapies’ which constitute modern precision medicine,” says senior author on the paper Antonio Giordano, M.D., Ph.D., director of the Sbarro Health Research Organization at Temple University.

The study revealed an important role of the cell cycle protein RBL2/p130 in triggering cancer cell death upon inhibition of AKT, which is hyperactive in many cancer types. The researchers found that RBL2/p130, a known tumor suppressor factor isolated by Giordano himself in the 1990s, is a direct target of the AKT kinase. The pharmacological inhibition of AKT led to RBL2/p130 protein stabilization, in both lung cancer and mesothelioma cell lines, and favored its localization to the cell nucleus, where it can function restricting cell proliferation, a well defined function of RBL2/p130 and of the other retinoblastoma proteins belonging to its family.

Further confirming the crucial role of RBL2/p130 in determining the cell response to AKT inhibition, the authors showed that AKT pharmacological inactivation no longer caused cancer cell death when RBL2/p130 expression was shut down through a specific silencing. Conversely, RBL2/p130 re-expression in previously silenced cells restored cell ability to undergo programmed death following AKT kinase inhibition.

AKT is a recognized target for antitumor strategies owing to its high levels in multiple tumors, and the manner in which it stimulates oncogenic pathways. Therefore, many companies have developed AKT inhibitors which are currently being tested in clinical trials. As RBL2/p130 is crucial in determining cancer cell fate upon AKT kinase inhibition, RBL2/p130 could serve as a predictive factor of the response to such a therapeutic strategy. The authors also assessed whether AKT pharmacological targeting could function in synergy with other approaches aimed at re-activating RBL2/p130 tumor suppressor function. The results confirmed that AKT inhibition functioned in synergy with cyclin dependent kinase (CDK) inhibitors in both preclinical models of lung cancer and mesothelioma. CDKs are the main kinases known to phosphorylate RBL2/p130, restraining its cell cycle-related tumor suppressor function.

“The combined use of these agents, AKT and CDK inhibitors, which converge on RBL2/p130 reactivation and are currently being investigated in the clinical setting, could help to reduce their dosage and consequently their associated toxicities,” says lead author Francesca Pentimalli of the National Cancer Institute of Naples Pascale Foundation, CROM.

“Our findings were conducted in lung cancer and mesothelioma, the latter being a tumor caused by exposure to asbestos, against which no curative approach exists,” says Giordano.  “However, given that RBL2/p130 is rarely mutated in cancer, but rather is mostly inactive by the action of AKT and CDK kinases, it is likely that this therapeutic strategy could work in a wider variety of tumors.”

The study, which was funded by the Italian Association for Cancer Research, the Sbarro Health Research Organization and the Mesothelioma Applied Research Foundation, stemmed from a productive collaboration between the University of Siena and the National Cancer Institute of Naples Pascale Foundation, CROM.

Original Newswise Release         PubMed Abstract

Virtual Reality: An Escape From Painful and Stressful Medical Treatments

Virtual reality (VR) technology allows users to immerse themselves in a three-dimensional computer-generated world, and despite being originally developed as an entertainment tool, over the last two decades VR has found a variety of applications in health care. Among these applications, which include treatment of phobias and anxiety disorders; cognitive and physical rehabilitation; pain management; treatment of eating disorders and obesity; surgical training and aid in surgical planning and performance, VR has shown promise in several clinical trials assessing its possible utility as a distraction tool to alleviate pain and distress during medical procedures.

A review article, recently published in The Clinical Journal of Pain, provides a comprehensive overview of the clinical studies using VR during several painful and stressful medical procedures, including burn injury treatments, chemotherapy, surgery, dental treatment, and other diagnostic and therapeutic procedures.

“VR has proven to be very effective in relieving pain, even in patients subjected to extremely painful procedures, who do not receive proper relief with pharmacological treatments alone,” says Antonio Giordano, M.D., Ph.D., of the Sbarro Health Research Organization at Temple University, and University of Siena, Italy, and corresponding author of the article. “Moreover, VR decreases cancer-related symptoms in different settings, including during chemotherapy. This is remarkable, considering that identifying interventions able to enhance treatment tolerance is crucial to improve both patients’ quality of life and compliance to therapies, which, in turn, can increase their chances of recovery.”

“Despite these promising results, we wanted to point out that further studies involving a greater number of patients are needed both to generalize the observations and to establish predictive factors to select patients who are more likely to benefit from VR,”  says study author Paola Indovina of the Institute for High Performance Computing and Networking, ICAR-CNR, Naples. “Moreover, more efforts should be put into the evaluation of changes in physiological factors, which might provide objective confirmations of the patients’ self-report measures. Also, more studies should explore VR efficacy after several repeated sessions to assess possible long-term benefits of the VR intervention.”

“It is also important to note that most studies so far used relatively low-tech VR systems compared to the state-of-the-art systems available on the market today, which are more immersive, more user-friendly, more portable, and much less expensive,” adds coauthor Giuseppe De Pietro, Director of the Institute for High Performance Computing and Networking, ICAR-CNR, Naples, Italy. “Therefore, VR has the potential both to become more effective and to find a more widespread use.”

Journal Reference:

Indovina P, Barone D, Gallo L, Chirico A, De Pietro G, Giordano A. Virtual reality as a distraction intervention to relieve pain and distress during medical procedures: a comprehensive literature review. Clin J Pain, 2018.

Original Newswise Release

Repurposed Parasite Drug New Weapon Against Mesothelioma

Anthelmintic drug already approved to treat infections of pinworm parasite was shown to effectively impair both mesothelioma cell growth and migration.

Mesothelioma, a very aggressive cancer, is mainly associated with exposure to asbestos. No effective therapies are currently available to treat mesothelioma, and the prognosis is extremely poor. Therefore, there is an urgent need to identify new possible therapeutic approaches.

Researchers challenged mesothelioma cells with pyrvinium pamoate, testing the potential to repurpose a drug already approved to treat infections of pinworm parasite. Analyzing at the molecular level, researchers found that the drug affected the expression of downstream genes in the WNT signaling pathway, which are implicated in mesothelioma aggressiveness and its resistance to conventional therapy.

Published in the Journal of Cell Physiology, the study was conducted by research groups lead by Dr. Antonio Giordano at the Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, with collaborators at the University of Siena, Italy.

“These are encouraging results, especially considering that drug repositioning, using already approved drugs for new indications, is a promising strategy to identify active molecules for a more rapid and less expensive clinical translation compared to de novo drug development,” says study author Marcella Barbarino of the University of Siena.

“The results of this study represent a step forward in the development of new treatments for patients with mesothelioma. Pyrvinium pamoate is able to affect important features of mesothelioma aggressiveness, suggesting that the repurposing of this drug for mesothelioma treatment could represent a new promising therapeutic approach,” says Giordano.

The study was funded by the Sbarro Health Research Organization (SHRO) and the Mesothelioma Applied Research Foundation, and is dedicated to the memory of Mr. Vittorio Stortino.

Journal Reference: Barbarino M, Cesari D, Intruglio R, Indovina P, Namargedi A, Bertolino FM, Bottaro ME, Delaram R, Bellan C, Giordano A. Possible repurposing of pyrvinium pamoate for the treatment of mesothelioma: a pre-clinical assessment. J Cell Physiol, 2018.

 Original Newswise Release                            PubMed Abstract

 

Diverse Role of CDK9 Gene in Cell Regulation Continues to Reveal Cancer Treatment Targets 25 Years After Discovery

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A gene discovered by Temple University researchers has proved to be an important target for cancer therapy, with the discovery of its roles in controlling cell proliferation, differentiation, apoptosis, and DNA repair. The mutli-functional kinase CDK9 (cyclin-dependent kinase 9) is considered a relatively tractable target for drug discovery and provides a route for the indirect targeting of other gene expression, such as MCL-1 and MYC, which themselves are implicated in cancer progression but are more challenging targets for drug discovery.

“If CDK9 is inhibited or blocked,” says Antonio Giordano, M.D., Ph.D., “it prevents the promotion of differentiation, suggesting that the inhibition of CDK9 leads to selective down-regulation of cell survival genes controlled by super enhancers such as MCL-1, MYC, and cyclin D1.”

The gene for CDK9 was first discovered by Giordano in 1994, the first of many studies of CDK9 developed at the Sbarro Institute for Cancer Research and Molecular Medicine at Temple University in Philadelphia. Over the past 25 years, CDK9 has proven to play many different roles. As discussed in a review published last week in the Journal of Experimental and Clinical Cancer Research, the functions of CDK9 include cellular differentiation, controlling processes such as transcription, balancing the process of cellular differentiation and apoptosis (programmed cell death), as well as regulating transcription of human immunodeficiencty virus (HIV), all of which suggests potential for targeting this kinase in cancer therapy to control or block key cellular processes.

To thoroughly assess the potential to leverage these multiple functions for combination therapies with CDK9, a variety of inhibitors have been investigated in preclinical and clinical studies. Results have demonstrated antiapoptotic and antitumor effects.

“This is important from a clinical point of view,” says Giordano, Director of the Sbarro Institute, where he is actively investigating the role of CDK9 inhibitors as therapeutics for a variety of hematologic cancers and solid tumors. Based on the body of research describing the role of CDK9 in acute myeloid leukemia (AML), Dr. Giordano suggests that, “targeting the CDK9 pathway, which is dysregulated in AML, is a very attractive approach.”

“Many studies demonstrate that dysregulation of the CDK9 pathway has been observed in human tumors such as lymphoma, prostate cancer, neuroblastoma and others,” says Dr. Silvia Boffo, PhD, research assistant professor at the Sbarro Institute, “and the CDK9-related pathway has emerged as a prioritized target for cancer therapy across a range of different tumor types.”

An immunologic role for CDK9 has also been discovered and was reported in Oncogene by Dr. Giordano, in collaboration with researchers at the University of Siena in Italy. They have shown that it interacts with gp130, the receptor of the Interleukin-6 (IL-6) family of cytokines. “This should allow us to take advantage of IL-6 as therapeutic agents for targeted therapy in selected histotypes of human cancer,” Giordano says.

“As CDK9 inhibitors are nonselective, predictive biomarkers that may help identify patients most likely to respond to CDK9 inhibitors are now being utilized, with the goal of improving efficacy and safety,” concludes Dr. Giordano.

Original Newswise release         Pubmed Abstract