416-440-7780
research@icrf.ca

Dr. Nir London

GDr. Nir London – The Weizmann Institute of Science

Project Title
Development of covalent therapeutics for the KRAS G12D oncogenic mutant

Research Topics
Colorectal Cancer, Lung Cancer, Pancreatic Cancer, Pediatric Cancer

Named Grant:

The Feldberg Family Project Grant

About the Investigator:

Dr. Nir London completed his PhD in computational structural biology at the Hebrew University of Jerusalem and post-doctoral fellowship at UCSF. Dr. London joined the Weizmann Institute of Science in 2015, where his lab is focused on covalent chemical biology and is developing new technologies to discover and functionalize covalently acting compounds. His honors include the Alon fellowship, the 2021 EFMC award for young medicinal chemist in academia and the 2021 ISCB award for young chemical biologist.

About the Research:

Cell growth and division are tightly controlled by a complex network of proteins that regulate these processes within and outside of cells. Disruptions or mutations in these proteins can lead to uncontrolled cell growth, resulting in cancer. Among the most significant oncogenic proteins is KRAS, where mutations keeping it in a continuously active state are frequently found in various cancers. These mutations are particularly prominent in pancreatic cancer. Developing molecules that can bind to and inhibit these active KRAS mutants are therefore a crucial goal for treating pancreatic and many other cancers.

Dr. London’s laboratory specializes in the development of covalent inhibitors, which are a type of molecule that binds irreversibly to a target protein. This project seeks to develop covalent inhibitors for KRAS G12D, the most common KRAS mutant in cancer. A major breakthrough recently occurred with the development of effective covalent inhibitors for G12C – a different, less abundant mutant. Prior to this, KRAS had long been considered “undruggable” due to its small size and other factors. Now, based on the structure of these molecules and using computational tools for inhibitor design developed by the lab, Dr. London will design, synthesize and test molecules with chemical groups that will react specifically with the G12D mutant. His team will select the best binders discovered in their initial experiments and test whether they inhibit KRAS G12D in cells and in biological experiments. The molecules developed will contribute the study of KRAS G12D biology and form a basis for the develop of potent drugs targeted against the G12D mutation. This research offers new hope for more efficacious and less toxic treatments urgently needed for treating pancreatic and other KRAS G12 cancers.

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Gilad Bachrach, PhD

Gilad Bachrach, PhD – Hebrew University of Jerusalem

Dr. Gilad Bachrach’s group investigates the role of bacteria in cancer development (BactriOncology), and are searching for ways to utilize bacteria for cancer detection and treatment. Dr. Bachrach received his B.S. in Biology, M.S. in Microbiology and his PhD in Clinical Microbiology in the Hebrew University of Jerusalem. He then followed to a post-doctorate in Molecular Microbiology at the National Institute of Medical Research in London followed with a year at the National Institute of Dental and Craniofacial Research (NIH) to gain experience in the field of Oral Microbiology prior to his return to the Hebrew University-Hadassah School of Dental Medicine where he is a professor today.

BacteriOncology, the study of bacterial involvement in cancer, is a rapidly advancing research field. Among its key players is Fusobacterium nucleatum, an oral bacterium primarily associated with periodontal disease. Surprisingly, F. nucleatum has been identified as overabundant in colorectal, esophageal, and pancreatic cancers, where its presence correlates with poor treatment outcomes.

Dr. Bachrach’s group was among the first to genetically manipulate this bacterium. Their previous ICRF-funded research demonstrated that F. nucleatum colonizes tumors by binding to the Gal-GalNAc sugar moiety, which is overexpressed on certain cancers. They further showed that F. nucleatum is prevalent in human breast cancer and selectively colonizes mammary tumors in mice, where it promotes tumor growth and metastasis. While antibiotic treatment effectively inhibits these effects, it can interfere with standard cancer therapies.

To overcome this challenge, the team is developing targeted strategies to combat F. nucleatum. Their current focus is on a fusobacterial protease they discovered, named FUSOLISIN, which they believe supports bacterial survival and promotes tumor growth. Preliminary results reveal that inhibiting FUSOLISIN not only kills intratumoral F. nucleatum but also triggers an inflammatory response that suppresses tumor progression. Dr. Bachrach’s team aims to develop specific FUSOLISIN inhibitors as a novel therapeutic approach to eradicate tumors colonized by fusobacteria.

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Rotenberg family offers hope to families through fundraising

The Rotenberg family—Debbie, Joel, Carly and Jordana

The Rotenberg family—Debbie, Joel, Carly and Jordana—has been involved with ICRF since 2007. It was that year that Debbie Rotenberg’s mother passed away. Her family and her brother’s family established the Shilamus Katchky Memorial Fund at ICRF Toronto in her honour. When her father passed in 2018, the fund was renamed the Shilamus and Max Katchky Memorial Fund.

“We would make annual donations to provide ongoing support to ICRF,” said Debbie Rotenberg.

But the family’s resolve to contribute to cancer research in Israel only strengthened when Carly was diagnosed with cancer at age 24. “Hers was unfortunate, horrible, bad luck. There was no explanation. It wasn’t genetic. It was sheer bad luck,” said Rotenberg.

In 2025, her husband Joel would encounter the same bad luck. “He was diagnosed with multiple myeloma in October,” said Rotenberg. “He was supposed to start chemo, but they had to admit him because his health was in crisis.”

The beloved husband and father’s diagnosis was changed to multiple myeloma/plasma cell leukemia, an extremely rare, quick, and fatal disease. Joel died within 11 days, on November 9. The family asked people to contribute to ICRF in his memory and they have been generously giving to the Shilamus and Max Katchky Memorial Fund ever since.

“Plasma cell leukemia has a very rapid course, providing little opportunity for researchers to study it,” said Debbie. “Providing financial support to the brilliant minds doing cancer research in Israel feels like a productive way to channel our grief.”

Since her late husband was a huge supporter of Israel and ICRF Toronto, Rotenberg knows Joel would be very proud of the funds their family and friends are raising. “He would feel it was very important to continue funding Israeli researchers,” said Rotenberg. “Our hope is that somebody else can be saved through their work.”

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Honouring a legacy of kindness, strength and hope

Rebecca and Alan Simpson with their children Kelly, Hannah and Jared.
Rebecca and Alan Simpson with their children Kelly, Hannah and Jared.

When Rebecca Simpson was diagnosed with breast cancer, she and her family were shocked. Despite regular screenings, the disease had already progressed to Stage 4 by the time of her diagnosis. In June 2025, the beloved wife and mother lost her long-running battle against cancer. To honour Rebecca’s life and legacy, her husband, Alan, along with their family, recently made a generous donation to ICRF to help fund research that leads to earlier detection and better treatments.

As Alan explains, Rebecca had a remarkable gift for making everyone around her feel valued and uplifted. “Supporting ICRF in her memory isn’t just about finding a cure—it’s about honouring her spirit of compassion, optimism, and love of life,” he says. “This gift is a way to continue her legacy of kindness, strength, and hope.”

Generously donating to ICRF was an easy choice, as Rebecca and Alan have always shared a deep love for Israel and the Jewish people. “Supporting ICRF brings together two causes close to our hearts—advancing world-class cancer research and doing so in Israel, a country known for its innovation and medical excellence. ICRF’s work represents hope, science, and the kind of impact Rebecca would have been proud of.”

Alan hopes this gift will inspire others to support cutting-edge cancer research and ensure that more people receive an early diagnosis and the chance for a cure. “If Rebecca’s story encourages even one person to take action, her light continues to make a difference.”

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In Conversation with Dr. Neil Berinstein

 

Jen: Welcome, Dr. Berinstein. Thank you for taking the time to chat with us today. Could you tell our readers a bit about your role as a clinician researcher in the field of oncology and hematology at Sunnybrook Hospital?

Dr. Berinstein: Thank you for having me. Certainly, my role as a clinician researcher is multifaceted. I spend half of my time dedicated to research, focusing particularly on hematologic malignancies, and exploring innovative approaches such as immunotherapy and targeted therapy. These targeted therapies are designed to specifically address the abnormal pathways within cancer cells, moving away from traditional cytotoxic drugs with their associated side effects.

Jen: Dr. Berinstein, can you tell me about your relationship to University of Toronto?

Dr. Berinstein: Yes, I’m a professor of medicine, but I’m also a professor of immunology at the University of Toronto. I’ve had a lab at the University of Toronto. I’ve had a dozen students over the years achieve their PhDs or masters in the department of Immunology, doing various types of basic immunology research. And at one point in my career, I was head of a global program sponsored by a pharmaceutical company to develop vaccines for cancer.

Jen: That sounds like fascinating work. Could you tell us more about your involvement in vaccine development for cancer and how it fits into the broader landscape of cancer treatment?

Dr. Berinstein: Certainly. I’ve been deeply involved in vaccine development for cancer, recognizing the tremendous potential of harnessing the immune system to target and eradicate cancer cells. While the field of immunotherapy has seen significant advancements with monoclonal antibodies and CAR T cells, vaccines for cancer remain a challenge. However, their potential for providing targeted and long-lasting protection is undeniable, like the efficacy we see with vaccines for infectious diseases like COVID-19 or the flu.

Jen: Dr. Berinstein, your translational research trials seem to be making significant strides in advancing lymphoma cancer treatment. Could you share more about the trials you’ve been leading and their impact on patient care?

Dr. Berinstein: Absolutely. I’ve been leading translational trials focused on diseases like diffuse large B cell lymphoma and Waldenström’s macroglobulinemia. These trials aim to bridge the gap between basic research and clinical outcomes, with a particular emphasis on identifying patient subsets that may benefit most from novel treatments. One trial is now in the results analysis phase.  We have a team, including a masters student, pouring through the clinical, biologic and immune data from this trial.  Through extensive biomarker analysis and collaboration with six centers across Canada and 25 patients, we’re striving to improve outcomes and tailor treatments to individual patients.  I really enjoy organizing trials even though they are a lot of work from start to finish.  It’s only when you’re “in the trenches” that you realize how complicated even a single clinical trial may be.

I am also working on another trial that involves 66 patients with ten centres across Canada.  This trial involves using a new targeted therapy in combination with some standard drugs that are used for Waldenstrom Macroglobulinemia. Because we are expected very strong clinical responses from this novel combination treatment we are collaborating with a well known biotechnoloby company to perform very sensitive molecular analyses of blood and bone marrow to document how deep these responses are.  We are alco collaborating with other researchers to look for novel gene mutations that may eventually be potential targets for new drugs.

Jen: It’s evident that your work encompasses both research and clinical care. How do you balance these responsibilities in your day-to-day life?

Dr. Berinstein: Balancing research and clinical care are indeed a complex task. My typical week involves seeing around 60 patients, conducting research, responding to patient inquiries, and engaging in teaching activities. While it’s challenging, having a structured schedule and a supportive team allows me to effectively manage these responsibilities and continue making meaningful contributions to both fields. I also participate in some review committees that evaluate new drugs that will eventually become available to cancer patients.

Jen: Can you tell our community about your involvement in Myeloma at Sunnybrook?

Dr. Berinstein: In the Odette Cancer Centre, my myeloma practice has significantly increased and  I’ve become the lead for our myeloma group.  I’ve written the guidelines that we use in our cancer centre for how we manage myeloma.  Myeloma is quite complicated because we have new drugs and different treatment paradigns continually .  The field is changing so rapidly because of research and advancements around the world that we often need to rewrite the guidelines every six months.

Jen: Dr. Berinstein, reflecting on your career, what achievements are you most proud of, both professionally and personally?

Dr. Berinstein: Professionally, I take pride in being able to contribute to cancer research and in my small way helping to contribute to some of the better understanding and treatment advances that have been  made in improving patient outcomes. From my involvement in vaccine development to leading translational trials and shaping treatment guidelines, each tiny milestone represents progress in the fight against cancer. Personally, I’m proud to see two of my children following in my footsteps, pursuing careers in medicine and research. I am glad that they wll have the opportunity to make contributions in their medical fields

Jen: Thank you, Dr. Berinstein, for sharing your insights and experiences with us. Your dedication to cancer research and patient care is truly inspiring.

Dr. Berenstein: It’s been my pleasure. Thank you for the opportunity to discuss the important work being done in the field of oncology and hematology and my connection to Israel Cancer Research Fund.  I really do feel that research is making, continues to make, and has made important, huge strides for people with cancer.  That is why I am such a big fan of the work that ICRF does, the answer to cancer really is research.

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CONTACT

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Fax: 416-487-8932
Email: donate@icrf.ca

ADDRESS

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Israel Cancer Research Fund | Charitable Registration #: 816102347RR0001