At the 2017 Annual Meeting for the Annual Association for Cancer Research (AACR), we presented research highlighting how we’re targeting PSMA – a marker on the surface of most prostate cancer cells – with radioimmunotherapy to kill cancer cells.
Radioimmunotherapy involves attaching radioactive particles to targeted immunotherapies that go directly to the cancer cells. The monoclonal antibody we use is called J591 and will bind only to PSMA. In this research, we attached the radioactive isotope actinium-225 (225Ac) to J591. We have used J591 linked with lutetium 177 (177Lu) and yttrium 90 (90Y) to treat patients in many clinical trials in the past. We believe that since 225Ac is an alpha particle emitter with much greater energy released that each individual antibody will lead to more tumor cell death. In our experimental models presented at the 2017 AACR meeting, 225Ac-J591 was not significantly more toxic than control (similar to placebo) in mice without tumors. When we treated mice with prostate cancer tumors, there was significant tumor killing following a single injection of 225Ac-J591.
Given our long history of administering radiolabeled J591 to hundreds of men in different clinical trials, we have plans to launch a phase I dose-escalation clinical trial (to determine safe doses and later look at tumor response) later this year. We and others are quite enthusiastic about this approach.
On June 29, Weill Cornell Medicine and NewYork-Presbyterian Hospital joined more than 270 institutions across the country in holding a Moonshot Summit. These summits were held in conjunction with Vice President Biden’s Moonshot initiative to fight cancer. On this national day of action, cancer experts throughout our institution, survivors, and advocates came together to share their ideas for increased collaboration and cures.
The summit conversation started with a constructive dialogue about clinical trials and the unfortunate fact that for many cancer types, the “standard of care” chemotherapies are not good enough. At Weill Cornell Medicine and NewYork-Presbyterian, immunotherapies and precision medicine are opening new doors in cancer treatment, but sadly not all patients currently have access to these types of cutting-edge treatments.
Clinical trials may have gotten a bad rap in the past, but they are a powerful tool to access innovative treatments. The speakers agreed that clinical trials should be easily accessible to all patients, but at times there are obstacles. These range from lengthy forms that deter enrollment, to bureaucracy that slows the timeline for opening new clinical trials, to disinterest and concerns about the treatments’ effectiveness. On a global scale, there has been a lack of adult participation in cancer clinical trials, while for children we actually see the opposite trend – very high enrollment. What can we learn from this information?
One of my colleagues Dr. Gail Roboz wisely stated, “I always tell my patients, be afraid of the disease, not the treatment.” She’s right in that we need to reframe the conversation to focus on making strides in increasing cure rates through new research that leads to new treatment breakthroughs across disease states.
We also talked about access to care. Not all patients are able to get a correct diagnosis quickly. This can be due to a variety of reasons including a lack of access to specialists, living in a rural area, or financial limitations. By increasing government research funding, as well as making it easier for patients to reach quality care, we can remove some of these barriers nationally. If we increase the number of people who are diagnosed with cancer early on, we can increase the cure rates. Additionally, as a country, we need to provide comprehensive care for patients and families and always put the interests of patients first. This includes offering supportive services beyond just the best medical care.
I felt so empowered by my colleagues and our patients’ great ideas about how we can overcome the challenges we face in cancer care. The Cancer Moonshot initiative is giving high hopes to many and will help ultimately change the world of cancer care as our country stands together with common goals and a renewed commitment to collaboration. By bringing everyone together at an event like this, we hear diverse perspectives and glean new insights. The fight against this terrible disease truly unites us all.
Advances in therapeutics have led to improvements in both survival and quality of life for patients with cancer, including men with advanced prostate cancer. Simultaneously, a number of cutting-edge scientific advances have been made in the underlying biology of advanced prostate cancer. There is great potential and power in integrating these new therapeutics and biomarkers, which is often referred to precision medicine. While great advances have already been made in this area, many remain highly sophisticated and restricted to selected centers, such as Weill Cornell Medicine and NewYork-Presbyterian Hospital, while others still need validation in a larger number of patients. Ultimately, the goal is to be able to bring these technologies and treatments to cancer patients all around the country and the world.
At the 2016 ASCO meeting, Dr. Himisha Beltran was the chair of a session entitled “Precision Medicine in Advanced Prostate Cancer: Understanding Genomics, Androgen Receptor Splice Variants, and Imaging Biomarkers.” This session intended to demystify some of the language and updates surrounding precision medicine.
Dr. Beltran spoke about important recent advances in tumor and patient genomics, such as the specific genetic alterations that we now know drive different types of tumors and play a role in the development of aggressive forms of the disease. The Cancer Genome Atlas (TCGA), a government-led initiative through the National Cancer Institute (NCI) has generated multi-dimensional maps for key genomic changes in 33 different types of cancer. It also provides a collaborative platform for physicians and researchers to search, download, and analyze data. Through the TCGA there have been critical discoveries regarding untreated primary prostate tumors with molecular classification of different subtypes that go beyond Gleason scores (the common way pathologists “grade” the aggressiveness of tumors).
Additionally, the first publication of the Stand Up to Cancer Prostate Cancer Dream Team demonstrated the genomic landscape of metastatic biopsies in the castration-resistant setting, which have differences compared to primary prostate tumors and fall into groups which may be targetable by certain therapies. Dr. Mark Rubin is the Weill Cornell Primary Investigator for the Stand Up to Cancer Dream Team. In addition, as follow up to Dr. Beltran’s initial 2011 publication, she detailed the results of Weill Cornell’s collaborative efforts leading to key discoveries in neuroendocrine and castration-resistant prostate cancer using tumor tissue as well as circulating tumor cell analysis.
Collaborator Dr. Gerhardt Attard presented data on utilizing DNA obtained from blood only, an emerging method of accessing the tumor’s genomic information in a non-invasive manner, which may decrease the need for a biopsy and allow for multiple samples to be assessed over time. One clinically relevant portion of his work, being done in collaboration with Drs. Beltran and Francesca DeMichelis, is ongoing through a Prostate Cancer Foundation – Movember Challenge Award grant. Together, we are leveraging our published genomic data on neuroendocrine and treatment-resistant prostate cancer with the circulating tumor DNA from blood technology to assess patients’ cancer status before, during, and after treatment.
In addition to improvements in tumor and blood-based biomarkers, imaging biomarkers are also being investigated. Dr. Michael Morris described standardizing the use of traditional scans to assess prostate cancer progression. In addition, there are a number of molecular imaging modalities that may demonstrate increased sensitivity in the detection of tumors as well as give insight into the biology of individual tumors, highlighted by prostate specific membrane imaging including the New York-based collaboration between Memorial Sloane Kettering Cancer Center and Weill Cornell Medicine investigators.