Scientists at Dana-Farber Cancer Institute and University of Texas Southwestern Medical Center Discovery suggests a new strategy for attacking high-profile but elusive target in cancer

Dana-Farber Cancer Institute and University of Texas Southwestern Medical Center scientists have presented drug developers with an unprecedented targeting of a highly dangerous molecular cause of cancer.

The study targets a mutant form of the protein KRAS. This specific protein has proven to be untouchable by current therapies despite it being commonly altered in human cancers. The researchers identified the KRAS’s basic structure as a “dimer.” Its ability to function depends on the composite of two similar or identical proteins. That being said, KRAS can’t work if it is not a dimer. This finding has raised the possibility that drugs that inhibit the mutant KRAS from forming a dimer could in turn impede the protein’s ability to drive cancer growth.

Pasi A. Jänne, MD, PhD, senior author of the new study stated, “The KRAS gene is one of the most frequently mutated genes in human cancers. It’s mutated in 20-25 percent of lung cancers, making it the largest genomic subtype of lung cancer, as well as in a large percentage of colon, pancreatic, and other cancers. That kind of prevalence has made the KRAS protein one of the prime targets for new therapies. So far, however, it has resisted targeting with small-molecule drugs.”

While drugs capable of blocking the process of forming protein dimers do not currently exist for cancer or any other disease, this discovery reported by Jänne and his colleagues could potentially ignite new research in this area, the study authors state.

The Lead Author of the study Chiara Ambrogio, PhD said, “Our findings suggest that dimerization appears to be an essential aspect of KRAS’s role within the cell.” Pasi A. Jänne added, “On the one hand, in the dimer formed by normal and mutant KRAS, the normal portion counteracts the negative effect of the mutant portion. At the same time, we’ve shown that dimerization is critical for KRAS mutants to be fully oncogenic, or cancer-causing. This reliance on dimerization suggests that disrupting dimerization with novel therapies may be an effective way of attacking some cancers at their root.”

The KRAS gene exists in two copies, and each is inherited from the parent. When one copy of KRAS is mutated, potentially speeding up cell growth, the normal copy then reins it back in. In the new study, researchers sought to understand how the normal copy achieves this restraining effect.

To learn more about this study, visit the Dana-Farber website.

The other co-lead authors of the study are Jens Köhler, MD, of Dana-Farber and Zhi-Wei Zhou, PhD, of University of Texas Southwestern Medical Center. David Santamaria, PhD, of the University of Bordeaux, France, is a co-senior author. Co-authors are Raymond Paranal, Jiaqi Li, Marzia Capelletti, PhD, Cristina Caffarra, PhD, and Shuai Li, MD, of Dana-Farber; Haiyun Wang, PhD, and Qi Lv, of Tongji University, China; Sudershan Gondi, PhD, John C. Hunter, and Jia Lu, PhD, of University of Texas Southwestern Medical Center; and Roberto Chiarle, MD, of Boston Children’s Hospital and the University of Torino, Italy.

Takeda Pharmaceuticals To Acquire TiGenix

Takeda Pharmaceutical Company recently announced its plan to acquire an advanced biopharmaceutical company developing novel stem cell therapies for serious medical conditions, TiGenix NV. This acquisition will expand Takeda’s late stage pipeline and leadership in gastroenterology, strengthening its presence in the United States specialty care market. Takeda Pharmaceutical Company will subsequently enter into an offer and support agreement with TiGenix. This acquisition will extend the existing collaboration between Takeda and TiGenix to develop and commercialize darvadstrocel, which has received a positive CHMP opinion to treat complex perianal fistulas in Crohn’s disease. This will facilitate a recommended potential voluntary public takeover bid for TiGenix. This deal has the unanimous support of the CEO and TiGenix board of directors. The acquisition is a natural extension of an already existing partnership agreement between Takeda and TiGenix. Together, they have aimed to created new treatment options for patients with gastrointestinal disorders.

“As a leader in gastroenterology, Takeda recognizes the complex physical, emotional and social barriers that people living with fistulizing Crohn’s disease experience,” said Andrew Plump, Chief Medical and Scientific Officer, Takeda. “Limited treatment options exist today and I believe we can be most effective in serving this population by working in collaboration with partners whose unique skill sets allow us to more efficiently explore innovative approaches, including stem cell therapies. I have had the opportunity to work alongside the TiGenix team throughout our collaboration and know that we have shared goals and varied, but complementary expertise. I am thrilled at the prospect of welcoming them as part of our organization.”

Dr. Harvey Berger is Appointed to the Dana-Farber Board of Trustees

On February 21, 2018, Dr. Harvey Berger, MD was appointed to the Board of Trustees at the Dana-Farber Cancer Institute. He is among six other newly appointed individuals who will serve on the Hospital’s governing body.

In addition to providing his leadership and expertise to the Dana-Farber team, Dr. Harvey Berger is the Executive Chairman of Medinol, Inc., a global interventional cardiovascular-device company. Dr. Berger joined the Medinol team in February of 2017. Prior to joining Medinol, Inc., he founded a global biotechnology company, ARIAD Pharmaceuticals, Inc., where he served as the company’s Chairman and Chief Executive Officer.

“As a governing trustee, I look forward to working closely with the outstanding leadership and trustees of the DFCI.  CEO, Laurie Glimcher, and Board chair, Josh Bekenstein, have set a clear vision for the Institute in a world of personalized cancer medicines. The DFCI is second-to-none among cancer institutes and brings clinical scholarship, outstanding basic and translational research, and a historic dedication to patients to its mission every day. Being selected to work with them is a special honor for me,” said Harvey Berger.

Dr. Berger adds an extensive portfolio of experience in cardiology, oncology and life sciences. He has held both academic and administrative positions at Yale University, Emory University and University of Pennsylvania. Dr. Berger has published over 150 original papers, editorials, and reviews in scientific and medical journal and serves as an Established Investigator of the American Heart Association.

Dana-Farber elaborates on the differences between Basic, Clinical and Translational Research: What’s the Difference?

“Research” is an exceedingly broad term. However, when considering medical research, there are important distinctions among the three principal types  — basic research, clinical research and translational research.

Basic research is evaluating to how nature works, translational research takes knowledge acquired from basic research and applies that in the development of solutions to medical problems. Clinical research takes those solutions and applies them in clinical trials and studies them. When combined, each form of research creates a continuous research cycle.

Science based “basic” research describes something that’s an essential starting point. Associate Professor of Medicine, Medical Oncology, at Dana-Farber Cancer Institute, David Frank, MD, explains “If you think of it in terms of construction, you can’t put up a beautiful, elegant house without first putting in a foundation. In science, if you don’t first understand the basic research, then you can’t move on to advanced applications.”

Basic medical research is usually performed by scientists with a PhD in fields like biology and chemistry, to name a few. They will typically seek to answer fundamental questions about the structures of DNA, cells, proteins, molecules, etc. learning how they work.

“Basic research is fundamentally curiosity-driven research. Think of that moment when an apple fell on Isaac Newton’s head. He thought to himself, ‘Why did that happen?’ and then went on to try to find the answer. That’s basic research,” notes Program Director, Chemical Biology at Dana-Farber Cancer Institute, Milka Kostic. To learn more about research, visit the Dana-Farber website.

Dana-Farber’s Year of Milestones – 2017

As 2017 comes to a close, Laurie H. Glimcher, MD, has completed her first full year as President and CEO of the Dana-Farber Cancer Institute. Under Gilmcher’s leadership, Dana-Farber has achieved many milestones in cancer science and medicine. Dana-Farber is one of the world leaders in leveraging the human immune system to fight cancer, and in 2017 its team of researchers demonstrated the effectiveness of the first-ever personalized cancer vaccine in a clinical trial for melanoma.

Each patient a part of its melanoma study achieved complete remission from advanced phases of the disease, either from the vaccine they developed or in combination with another immunotherapy. These findings marked a transformation for cancer research. Dana-Farber remains as determined as ever to keep expanding the benefits of such discoveries to more patients.

Dana-Farber has been pivotal to drug development. Of the 75 cancer drugs approved by the FDA since 2011, Dana-Farber has been deeply involved in nearly half—including the recent landmark approval of CAR T-cell therapy, a new immunotherapy, for adults with non-Hodgkin lymphoma.

Dana-Farber currently has 900 clinical trials of various innovative therapies underway. Only select trials are supported by federal funding, the rest are available to patients because of the support Dana-Farber receives from its partners. Dana-Farber is considered a prestigious cancer center because it not only offers a commitment to research but also to patient care. Its success and commitment to its patients was recognized by Becker’s Hospital Review when they named Dana-Farber one of the 100 Great Hospitals in America for 2017.

NIH partners with 11 leading biopharmaceutical companies to accelerate the development of new cancer immunotherapy strategies for more patients

In late 2017, The National Institutes of Health and 11 leading biopharmaceutical companies started the Partnership for Accelerating Cancer Therapies (PACT). PACT is a five-year, $215 million, public-private research collaboration that is part of the Cancer Moonshot. PACT’s initial efforts will be focused on identifying, developing and validating robust biomarkers with the goal of advancing new immunotherapy treatments that harness the immune system to attack cancer. The PACT partnership will be managed by the Foundation for the National Institutes of Health (FNIH) and the Food and Drug Administration serving in an advisory role.

Eric Hargan, Acting Health and Human Services Secretary stated, “This new public-private partnership is a significant step forward in the battle against cancer and a real boost to the potential of immunotherapy. We are excited for this partnership, which will strengthen efforts already underway across HHS.”

“We have seen dramatic responses from immunotherapy, often eradicating cancer completely for some cancer patients,” said NIH Director Francis S. Collins, M.D., Ph.D.  “We need to bring that kind of success — and hope — for more people and more types of cancers, and we need to do it quickly. A systematic approach like PACT will help us to achieve success faster.”

This partnership will help to increase the overall understanding of response mechanisms and resistance to cancer therapy by facilitating systematic and uniform clinical testing of biomarkers. PACT’s research will define a set of standardized biomarkers to be tested across a variety of studies allowing them to be integrated into immune and other related oncology biomarkers into clinical trials.

In addition, PACT will facilitate information sharing amongst stakeholders to better coordinate clinical efforts, align investigative approaches, reduce duplication and enable more high-quality trials to be conducted. The constant gene uniform and harmonized assays will be facilitated in support of data reproducibility, comparability of data across trials, and discovery and validation of new biomarkers for immunotherapy and related combinations.

FNIH President and Executive Director Maria C. Freire, Ph.D. stated, “A scientific and organizational challenge this complex cannot be addressed effectively by any one organization acting alone. Instead, it requires the energies and resources of public and private partners working in close collaboration.”

Dr. Harvey Berger Discusses Ponatinib

Ariad Pharma CEO on Latest Leukemia Data from CNBC.

Dr. Harvey Berger discusses ponatinib, an oral drug developed by ARIAD to treat chronic myeloid leukemia(CML) and Philadelphia chromosome positive acute lymphoblastic leukemia (ALL). Ponatinib was designed to treat the resistant and tolerant forms of CML helping patients who have a mutation resistant to other cancer therapies.

ARIAD collaborators presented compelling clinical data about ponatinib at the American Society of Clinical Oncologists Meeting. Dr. Berger stated that “Well over one half of the patients who have failed every other CML drug, and had a very difficult time with their disease, now have a new treatment that will make a big difference in their lives.”

ARIAD collaborators presented compelling data about ponatinib and Dr. Harvey Berger has made numerous statements about this data at several points throughout the past few years. For instance, Dr. Berger stated, “Well over one half of the patients who have failed every other CML drug, and had a very difficult time with their disease, now have a new treatment that will make a big difference in their lives.”

Ponatinib was approved by the FDA on December 14, 2012, for patients with resistant or intolerant CML and Ph+ ALL. The approval was under the FDA Accelerated Approval program which required ARIAD to carry out additional studies. The FDA then granted full approval in 2016 that included a label update to Ponatinib.


Medinol Announces First Commercial Implantations of EluNIR™ Ridaforolimus-Eluting Coronary Stent System

Medinol announced that it obtained CE-mark for EluNIR™, its novel Drug Eluting Stent. This stent features a unique design to optimize clinical outcomes. The EluNIR will feature a low metal footprint and a proprietary elastomeric coating. EluNIR has demonstrated impressive outcomes in two randomized pivotal studies.

Medinol’s Chief Scientific Officer, Dr. Yoram Richter, stated “EluNIR is the culmination of over 20 years of Medinol research, development and science dedicated to improving clinical outcomes with coronary stent systems. Given the excellent results we have observed in our clinical studies for EluNIR, and the renewed focus on metallic drug eluting stents, we are excited to bring EluNIR to the European interventional cardiology community as physicians continue to drive towards optimizing results for their patients.”

Dr. Alaide Chieffo noted, “Our first cases were very successful and the EluNIR stent system with its metallic spring tip demonstrated high deliverability. The first case involved LAD disease distal to a very tortuous LIMA. The second case involved a severely calcified and diseased LAD that could not be crossed with another new generation DES despite lesion preparation with Rotablator, and was successfully treated with EluNIR. In a third case, the lesion was in a proximal RCA with unfavorable take-off and insufficient guiding-catheter support, and was also treated nicely with EluNIR. I have confidence in the longer term outcome as we continue to follow the patient’s’ progress.”

EluNIR will be available to select centers in Europe and other locations by late 2017. In 2018, a full range of sizes will be available. The EluNIR Stent System is an investigational device, not available for sale in the United States and Japan.

Laurie H. Glimcher, MD is Recognized for Excellence at AAMC Annual Meeting

During Learn Serve Lead 2017, the AAMC Annual Meeting in Boston, Laurie H. Glimcher, MD, was honored by the AAMC (Association of American Medical Colleges) with the prestigious Award for Distinguished Research in Biomedical Sciences. Laurie was among eight others recognized for outstanding contributions to academic medicine at the meeting. Laurie currently serves as the Dana-Farber Cancer Institute President and Chief Executive Officer.

The award given to Dr. Glimcher was for Distinguished Research in the Biomedical Sciences, honoring outstanding medical research related to health and disease. To earn this award, the research recognized should have a positive impact on medicine and the health of patients and populations. The AAMC has awarded this particular research prize since 1947.

Dr. Glimcher has uncovered unprecedented findings. Most notably, her research and discovery have impacted the advancement of cancer, asthma and osteoporosis. Dr. Glimcher is a distinguished leader in academic medicine, previously serving as dean of Weill Cornell Medical College. Her pioneering research has awarded her the position of international authority on the development and activation of lymphocytes in the immune system.

Dr. Harvey Berger Reflects on his Time at Yale School of Medicine

Dr. Harvey Berger recently celebrated his 40th anniversary of graduation from Yale School of Medicine. He was given the opportunity to reflect on his career and the time that he spent at the institution that helped get him started. Dr. Berger attributes Yale as the foundation of his success, and often expresses his gratitude for his years at Yale as a medical student, house officer, fellow and faculty member. Yale Alumni and Friends in Medicine recently interviewed Dr. Berger and shared his thoughts about Yale in their online publication. Yale’s current Dean, Bob Alpern, has had an influential impact on the medical school and its relationship with Yale-New Haven Hospital. Dr. Berger is proud to be part of such an amazing institution dedicated to educating future leaders in medicine, public health and biomedical science.