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Prof. Nadir Arber

Prof. Nadir Arber

Nadir Arber, MD, MHA, MSc

Dr. Arber, is an outstanding researcher and physician, expert in internal medicine, gastroenterology, health promotion and cancer prevention. He has changed the landscape of cancer prevention and management in Israel, by establishing the first integrated cancer prevention center at Tel Aviv Medical Center and by leading cutting-edge, out-side of the box, translational research in the field of cancer therapy. Dr. Arber’s world-wide reputation among the health care providers in Israel and in the world, based on his publications and achievements.

Nadir Arber (MD, MSc, MHA) is a full Professor of medicine and gastroenterology in Tel Aviv Medical Center and Tel Aviv University, Sackler School of Medicine. He is Yechiel and Helen Lieber Professor for Cancer Research. He had graduated medical school in Hadassah, Jerusalem, in 1987 (graduating Magna Cum Laude). He had done residency in internal medicine in Rabin Medical Center (1987-1991), and fellowship in gastroenterology in the Tel Aviv Medical Center (1991-1993). He had completed his MSc in 1990 and MBA in 1991. He also had three years of research fellowship at the Comprehensive Cancer Center at Columbia University, NY, at the laboratory of Dr. Bernard Weinstein, leader and director of the center (1993-1996).

The following are the milestones of his career:
In 1999, he was nominated to head the GI Oncology Unit at the department of gastroenterology.
In 2002-2008 he had headed the MD thesis committee, at Tel-Aviv University Sackler Medical School
In 2008 – 2014 he had headed the grants committee of the Sackler School of Medicine in Tel Aviv University.
In 2006, he established the unique Integrated Cancer Prevention Center at the Tel Aviv Medical Center.
from 2010-2017 he became the director of the cancer research center of Tel Aviv University.
Since 2011 he is the chief of the Djerassi-Ellias oncology center.
In 2014-2017 he established the Dotan hemato-oncology center in Tel Aviv University.
In 2014 he was the president elect of the Israeli society of gastroenterology and hepatology.
In 2015-2017 he served as the president of the Israeli society of gastroenterology and hepatology.
In 2018 he was chosen to lead the cancer prevention section at the European Society of Medical Oncology (ESMO)

In addition to the above, Dr. Arber has been serving on numerous international committees:
1. Scientific committee of the United European Gastroenterology Federation (UEGF)
2. Steering committee of the Association of National European and Mediterranean Societies of Gastroenterology (ASNEMGE)
3. Chairing the education committee of the ASNEMGE
4. Scientific committee of the European Society Medical Oncology (ESMO-GI)
5. Scientific committee of the American Society Medical Oncology (ASCO-GI)
6. Scientific committee of the Organization Mondale Entero Digestive (OMED(
7. Scientific committee of the World gastroenterology Organization (WGO)
8. Co-Chairing Organization for Oncology and translational Research (OOTR)

Dr. Arber is an outstanding researcher. Furthermore, he has obtained many national and international research grants and awards (>100) and has developed joint research projects world-wide.

Notably are his significant contributions to the field of cancer research, and in particular bringing the bench to the bedside. He is one of those few physicians that are willing to be deeply involved in both fields of clinical research combined with top quality basic science publications. His abilities of performing translation medicine put him at the forefront in the field of cancer. Hence, he has become a reference for many scientists.

Dr. Arber has been well recognized in the societies of gastroenterology and GI oncology. Dr. Arber has always been not only a leading physician but also a good scientist. Hence, he is a reviewer of the major journals and grants committees. He has been invited to present his findings at many important conferences world-wide. In the last three decades, Dr. Arber’s had oral presentations every year during these meetings, a task that is not easy to achieve in our competitive society. His presentations are exceptional original with the ability to point out the most important issues in an elegant and practical way.

Dr. Arber is highly intelligent, with excellent manners, boundless energy, integrity and outstanding knowledge in many fields of cell and molecular cancer biology. He performed excellent scientific work and was involved in numerous important research projects. He is collaborating with significant number of leading laboratories and scientists; Bert Vogelstein in Johns Hopkins, Anil Rustgi at U Penn, Alfred Nuegut and Hanina Hibshoosh at Columbia University in NYC, Steve Meltzer U of Maryland, Bernard Levin Prof emeritus at MD Anderson Cancer Center, Ray DuBois in Arizona, Rick Boland at Baylor, David Lieberman at Oregon, Andrew Chan and Daniel Chung at Harvard. He has been working closely with investigators across Europe and Asia, and in particular very big grants from the EU. He has established and led a consortium of investigators and clinicians involved in clinical and basic research.

Dr. Arber is heavily involved in teaching. He is the mentor of so many MD students doing their dissertation, as well as MSc and PhD students at the Sackler School of Medicine. Dr. Arber guides students in methodical, impressive ways that ultimately contribute to efficient learning. Dr. Arber is a clever, self-driven, thorough, hard-worker who possesses a novel scientific understanding.

He has authored significant number of important publications (~350) in high rank journals. His findings have been extensively cited and have been referred many times in important review articles. He has been working on the fascinating subject of cell cycle control and cancer development for many years the research team of Dr. Arber has diverse and broad experience in translational research focused on early detection, prevention and therapy of cancer, particularly in tumors of the gastrointestinal (GI) tract. The team is highly experienced in clinical studies, molecular epidemiology as well as in molecular and cell biology studies of cancer.

Currently, on-going research focuses on translational research, bridging between basic researches in the lab and clinicians and patients in the clinical center. The center has a long history of planning, developing, and conducting clinical trials, with a main focus on investigator-initiated and cooperative group trials investigating the activity of drugs for the prevention and treatment of GI malignancies and in particular colorectal cancer (CRC).

In the clinical grounds he is a real pioneer in the field of cancer prevention, by establishing the first integrative center where healthy individuals can be screened, for all/most cancers, on the same place and on the same day. One stop shop. Scientific wise he is thinking out side of the box trying to find novel cancer therapies. He is brilliant, innovative, open minded and most of all, humble and well-liked by his patients and by his peers. He is a motivated self-driven individual and an admirable team player. His research has the potential to change the practice of cancer therapy, by prevention and outside of the box novel therapies.


Detailed report on Dr Arber’s GI Cancer Research

1. CD24: A novel target for therapy

Antibodies are useful in cancer therapy because they can recognize tumor-associated antigens expressed at higher density on malignant compared to normal cells and can be used as a single therapy or in combination with traditional drug therapies. A large variety of mAbs have been developed. However, very few are able to kill a sufficient number of cancer cells and cause tumor regression in preclinical models, and even fewer are clinically useful in humans. This project centers on the use of humanized anti-CD24 mAbs with enhanced efficacy of anti-tumor activity. CD24, a mucin-like cell surface protein and P-selectin ligand, is a novel biological target for detection and treatment of cancer and therefore unique. In terms of CD24 expression, Dr. Arber found that CD24 was expressed in 90.7% of adenomas (benign tumor) and in 86.3% of carcinomas (malignant tumor). Furthermore, a normal human tissue array was performed in order to characterize the expression pattern of CD24 in normal human tissues. 32 types of normal human organs were included based on FDA guidelines, where each organ was taken from 3 normal human individuals. Anti-CD24 antibody was used to detect CD24 expression, confirming that the vast majority of normal tissues do not express CD24.

Anti-CD24 mAb treatment induces a significant growth inhibition of cancer cell lines, in a time- and dose-dependent manner. Xenograft models in vivo showed that tumor growth was significantly reduced in mAb-treated mice. Novel anti-CD24 toxin-conjugated mAbs were highly potent and cytotoxic to cancer cells. Using genetic engineering techniques the affinity and pharmacokinetic properties of the antibodies was significantly improved. In carefully conducted toxicity studies in small animals the mAb had no toxicity what so ever. To this extent, CD24 seems to be an ideal target for novel therapy. Several derivatives of the humanized anti-CD24 Abs were constructed. From the full IgG variant to the small fragments of the antibody (such as Fab and scFv derivatives), non-armed antibody and the conjugated forms that can served as therapeutic and diagnostic tools for CD24-expressing malignancies. Finally, Dr. Arber was able to produce bispecific antibodies against CD24 and CD30, as a proof of concept in the setting of hematological malignancies. Bispecific antibodies (bsAbs) can improve efficacy and decrease toxicity by targeting two targets on the same cell even at low level with moderate affinity. Hence, malignancies that cannot be effectively targeted with the individual mAbs may be effectively targeted by co-engagement of the two targets by the same mAb.

2. Gene Therapy using the Trojan Horse Strategy

In previous studies Dr. Arber has shown that recombinant adenovirus, that carries a lethal gene can induce rapid and effective cell death, using two active signal transduction pathways (Ras and β-catenin) that are active in malignant cells but not in normal cells. Hence, selective killing of tumor cells using the active mutations that caused the normal cells to turn into malignant cells is possible. Using this modality impressive growth suppress of human colon, gastric, hepatic and prostate cancer cells that display the respective hyperactive signaling pathway was achieved. The breakthrough provides a unique strategy for selective and effective eradication of the cancer cells with an active protection of the normal cells. The strategy should nbe effective in eradication of micro metastasis and even single cancer cell. The main novelty is that it is a universal system that can be used as a platform depending on the genetic profile and type of cancer.

3. The “Humanized” Chicken Embryo Chorioallantoic Membrane (CAM) as a personalized platform for screening of cancer therapeutics

The idea behind this study is to make an important contribution to the advancement of personalized medicine. It is aim to develop a cost-effective model that similarly mimics tumor biology and enables improved screening platform for drug discovery with a maximum patient compliance. Implementation of alternative models to simplify screening of newly developed potential treatments, whose numbers are growing, is mandatory especially due to the ethical concerns involved with in vivo studies. The CAM-based approach provides high-fidelity technique that translates basic research to the clinic.

Predicting clinical response to anticancer drugs remains a major challenge in cancer treatment. Every day, millions of people are taking medications that will not help them. “Personalized medicine,” is the tailoring of medical treatment to a single person, shape his response to a particular treatment and aims to better target intervention, maximize benefit and minimize harm. Several techniques are available to grow primary cell cultures from tumors; however, very few have been found to be promising. The current approach suggests a cost-effective model that similarly mimic tumor biology and provide faster information on the activity of anticancer therapies and could therefore make an important contribution to the advancement of personalized medicine. Animal experiments are the cornerstone of cancer research. Nude mice and patient-derived xenograft tumor (PDXT) models are expensive, long in nature and painful. By using the suggested CAM strategy one can efficiently study diseases and testing anti-cancer products that replace animals and relevant to human health. The CAM is naturally immuno-deficient and rich in vascularity therefore an ideal system, allowing to generate 3D cancerous “organoids” in a very efficient, reproducible and cost-effective manner and translates basic research to the clinic. It is therefore an attractive model to rapidly assess the effectiveness of novel candidate therapeutic drugs.

4. CD24 improves wound healing

Dr. Arber, in several elegant studies has shown that CD24 has an important role in wound healing. The underlying hypothesis is that CD24 plays a key role in cell proliferation, adhesion and migration of healthy cells to the damaged area to restore normal tissue in the wound healing process. Dr. Arber was able to produce ointment containing CD 24, and this project is advancing for clinical use.

5. CD24 as a novel biomarker for cancer

Dr. Arber team is developing a blood test that can be used for early detection of cancer. In this study the utility of CD24 expression levels in peripheral blood leukocytes is used for the detection of individuals with pre-malignant and malignant solid and hematology malignancies.

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