Targeted Cancer Therapy

Since cancer involves the rapid reproduction of cells, most forms of treatment, like chemotherapy, target and kill rapidly dividing cells, regardless of whether or not they’re cancerous. Targeted therapy, also known as a form of precision medicine, is a new type of treatment that is becoming a focus in cancer research because it works on stopping and killing cancer cells without harming other cells, a common issue with chemotherapy.

Precision medicine involves treating a patient’s tumor based on the genetic change in the cancer cells (either in malignant blood cells or in the solid tumors themselves) and interfering with proteins that help cancers grow and spread. These medications work in a variety of ways to target the cancer, including helping the immune system destroy cancer cells, stopping the cancer cells from growing, killing the cancer cells and starving the cancer of stimulants (such as hormones)  it needs to reproduce and grow.

This therapy requires doctors to have a genetic understanding of the cancer and allows for more personalized treatment.  In some cancers like non-small cell lung cancer, forms of chronic leukemia, and types of breast cancer, these molecularly targeted therapies have become a standard of care.  It also is being studied in many clinical trials with extremely positive results. In order to receive these treatments, a patient must undergo a test to see if the genetic change being targeted is present in their tumor. This test is often a blood sample or a biopsy where the doctor removes a sample of the cancer and then the DNA is sequenced to look for genetic changes. If the changes match the targets of the therapy, the patient may be a good candidate to receive the drug. The results have been extremely promising and indicate that this may be an area where many new discoveries are made in the coming years. Several targeted medicines (such as ponatinib and brigatinib) have been approved and are widely used by patients whose cancers have been genetically defined.

What is CAR-T Cell Therapy?

Doctors have been fighting cancer for decades, but until now most treatment has been based largely on chemotherapy and surgery. One of the new avenues cancer researchers are exploring is CAR-T cell therapy, with the hope that it will provide more personalized treatment for cancer patients.

CAR-T cell therapy, sometimes described as a “living drug,” works by extracting the patient’s T cells, which are the cells that recognize and kill infected cells, and modifying them so they’re better able to fight cancer. 

In order to create CAR-T cell therapy, some of the patient’s blood is taken and the T cells are separated and then genetically modified. Through the modification process, the cells produce receptors on their surface called chimeric antigen receptors, or CARs, which allow the cells to recognize and attach to a specific protein on the tumor cells. When the cells are reintroduced to the patient’s body, they multiply, recognize the cancer cells and then kill them.

As of 2017, two CAR-T cell therapies have been approved by the FDA as a standard treatment option, including one for the treatment of children with acute lymphoblastic leukemia (ALL) and the other for adults with advanced B-cell lymphoma (DLBCL). CAR-T cell therapy has expanded the range of options for patients who previously didn’t have many therapeutic choices. For example, those with ALL who suffered a relapse after intense chemotherapy or a stem cell transplant usually did not have another way to fight the disease, but CAR-T cell therapy can now offer them another highly effective option.  The greatest challenge is managing the potential toxicities of these CAR-T therapies when given to patients with these blood cancers. Physicians are working diligently to try to apply CAR-T treatment to patients with solid tumors.  So far, efficacy has been limited. 

Nicole Elizabeth Berger’s Exciting Year

It’s half way into year and already 2018 has been a whirlwind for Nicole Elizabeth Berger. Nicole starred in the recently released film, All At Once. All At Once is a family drama that focuses on an upcoming artist whose life is turned around when he gained guardianship of two young girls after their parents, who were his best friends, were killed in 9/11. The film was originally shown at the Napa Valley Film Festival in 2016 and was released for streaming and DVD in April 2018.

Nicole recently wrapped up filming Clover in Buffalo, NY. Clover is a dramatic crime film about two brother who have to go on the run and protect a teenage girl who is witness to a murder. Nicole plays the film’s namesake, Clover. The film is set to release in early 2019.

Nicole also just finished filming a fantasy-reality film, The Place of No Words. The film centers around 3-year-old, Bodhi, as he battles the complexities of an adult world with his father. The film takes place in Snowdonia, Wales and Nicole plays Esmeralda, a fairy who interacts with the characters in the film.

When Nicole isn’t on set, she is attending Palm Beach Day Academy in Palm Beach, Florida, and partakes in the school’s theater program. This May, she played Maria in the school’s production of West Side Story. Last year, she starred as Ms. Honey in the school’s production of Matilda. In May, she also was awarded top drama award for a graduating senior at Palm Beach Day Academy, the Amory L. Haskell Award.

 

Boys & Girls Clubs of Palm Beach County Start Construction on New Teen Center

Harvey Berger gives back to many organizations he is dedicated to, especially to those in his local community. The Boys and Girls Club of Palm Beach County works with young people to reach their potential and make sure they are on track to graduate from high school. After reaching a $6 million fundraising goal, the organization has broken ground for phase 1 of the Smith & Moore Family Teen Center that will open in Belle Glade.

Plans for the new Teen Center were put into motion after the current location found themselves forced to turn away young people every day because it lacked the facilities and staff, only being able to serve 321 members. The Smith & Moore Family Teen Center will be able to offer academic, social and cultural activities for 900 members and will offer career prep programs.

“We are going to set the standard as the number one advocate for Belle Glade youth during out-of-school time.”- Jaene Miranda, president and CEO of BGCPBC

In mid-April, the Boys & Girls Club of Palm Beach held a ceremonial groundbreaking. The new state-of-the-art location will be two-stories, 13,000 square feet, and provide necessary after-school resources for the Belle Glade youth. BGCPBC is now ready to move to phase 2 of the $10 million campaign and is now looking to raise an additional $4 million to go towards an endowment fund that will keep the facility up and running.

Radioimmunotherapy | An Overview

Radioimmunotherapy is a combination of both radiation therapy and immunotherapy. Immunotherapy refers to treatments that use the body’s own immune system to combat cancer.

Several specific types of immunotherapy engage monoclonal antibodies. These antibodies then target select antigens that exist on the surface of cancer cells. They will then attach to cancer cells and act as a “disease-fighters” in the immune system.
Monoclonal antibodies, without radionuclides attached, are commonly used to treat cancer. These monoclonal antibodies are called “naked antibodies.” When conjugated or attached, monoclonal antibodies are paired with a radioactive substance and injected into the bloodstream. When used in radioimmunotherapy, they often travel and bind to cancer cells and deliver high doses of radiation directly to tumor cells. These conjugated monoclonal antibodies will then target the antigen directly. This specific approach is notably less damaging to the existing normal cells in other parts of the body as opposed to naked antibodies.

Radiolabeled antibodies such as ibritumomab tiuxetan attach to the CD20 antigen found on lymphocytes when treating non-Hodgkin lymphoma. Lymphoma starts in the a type of white blood cells known as lymphocytes and will then travel throughout the body and settle into several places, simultaneously.

Notably, researchers have begun studying antibody pairings with different radioactive agents and their potential uses in treating many other blood cancers or solid tumors. These cancers include prostate cancer, melanoma, ovarian cancer, leukemia, high-grade brain glioma, and colorectal cancer.

How Clinical Trials Advance Cancer

Dana-Farber Cancer Institute’s Director of the Early Drug Development Center, Geoffrey Shapiro, MD, PhD, addressed many questions that individuals often have regarding clinical trials. Additionally, he discussed how cancer treatment overall can be improved. The DFCI’s Early Drug Development Center specializes in conducting phase I clinical trials.

Shapiro discussed the importance of clinical trials noting that they are they are necessary in determining the safety and efficacy of new cancer drugs or drug combinations. He specifically noted the degree of care and attention to control necessary to generate a substantial enough amount of data that will ultimately allow medical scientists the ability to determine whether a drug is safe, what the appropriate dosage should be, and how effective the drug is.

When considering the advances made in clinical trials, Shapiro highlighted cell-cycle related agents, including CDK inhibitors. CDK inhibitors can prevent the proliferation of cancer cells and have transformed the treatment of estrogen receptor-positive breast cancer. Shapiro and his team are now extending the uses of these drugs to other diseases, including lung cancer, glioblastoma, and some forms of lymphoma and sarcoma.

While DFCI does extremely well in filling its clinical trials, nationally, the percentage of cancer patients participating in trials is alarmingly low. One of the most meaningful ways cancer patients can impact and continue to progress cancer treatment is by enrolling in a clinical trial. To learn more about Dana-Farber’s clinical trials, read Shapiro’s full interview.

The First U.S. Commercial Implants of Innovative EluNIR™ Drug-Eluting Stent Announced

In early January, Medinol and Cordis announced that the EluNIR™ drug-eluting stent (DES) was used commercially for the first time in cases in the United States. The procedures using the EluNIR™ were performed at two prestigious hospitals, New York-Presbyterian Hospital/Columbia University Medical Center and the Piedmont Heart Institute.

Medinol’s Executive Chairman, Harvey Berger, M.D., stated that the commercial launch of the EluNIR drug-eluting stent is a major step forward for Medinol and for patients with obstructive coronary artery disease.  This new stent system has important advantages for interventional cardiologists who are always looking for better and more effective ways to safely open occluded or narrowed vessels. Harvey Berger, M.D. to work with Medinol’s core business of interventional cardiovascular devices, in addition to its businesses developing sub-millimeter implantable sensors, unique percutaneous aortic valves and other complementary products.

The New York-Presbyterian Hospital/Columbia University Medical Center’s Director for Interventional Vascular Therapy, Martin B. Leon, M.D., noted, “Our first patient cases with the EluNIR™ stent went perfectly and we are enthusiastic about the overall performance including the uniform vessel coverage and the delivery system with the metallic spring tip, which is unlike any other product in the market. I have been following Medinol for over 20 years and am excited to see yet another one of the company’s innovative products launch in the U.S. market.”

The EluNIR™ stent was approved for the treatment of patients with narrowing or blockages to their coronary arteries. It is currently being distributed to cath labs throughout the United States by Cordis. The stent system is designed to help clinicians easily deliver this new DES in highly complex anatomy and disease.

“The physicians and staff at Columbia and Piedmont have played pivotal roles in the evolution of the EluNIR™ stent,” said Dr. Yoram Richter, chief scientific officer at Medinol. “We are honored to have the first commercial cases with EluNIR™ performed at such notable institutions. This event marks another step in Medinol’s legacy, which has continued to stretch the limits of innovation, starting with our NIR stent in 1996.”

Under a long-term distribution agreement between Cardinal Health and Medinol, Cordis was given Cardinal Health’s interventional vascular business, which includes the rights to sell Medinol’s coronary stent portfolio. This portfolio now includes the EluNIR™.

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.