2018 in Review: Advancements and Accomplishments

From delivering exceptional care in the clinic, to presenting at scientific conferences and publishing research in high-impact medical journals, our Genitourinary (GU) Oncology Program had an exceptionally busy 2018. We continue to work diligently to develop new and more effective therapies to treat advanced prostate, bladder and kidney cancers, while educating the community about cutting-edge advancements in the field.

As we look back on 2018, we wish to share a brief update of our research and accomplishments. Here’s what our team has been up to over the past year.

New Faces
Most recently, we were proud to welcome Dr. Cora Sternberg, a global thought-leader in the GU oncology space, to our team. Dr. Sternberg will facilitate the continued growth and development of clinical and translational research programs in GU malignancies, as well as serve as Clinical Director of the Englander Institute for Precision Medicine (EIPM) to develop strategies to incorporate genomic sequencing and precision medicine within our Program and across Weill Cornell Medicine and NewYork-Presbyterian.


New Events
More than 200 prostate cancer patients and loved ones attended our inaugural New York City Prostate Cancer Summit, a multi-institutional collaboration between Weill Cornell Medicine, NewYork-Presbyterian Hospital, Columbia University Irving Medical Center and Memorial Sloan Kettering Cancer Center. This educational and advocacy event featured presentations and panel discussions from local medical experts and national advocacy leaders, with topics including nutrition, screening, coping and anxiety, immunotherapy and much more. Our second annual Summit is slated for September 2019 during Prostate Cancer Awareness Month. Stay tuned for details.


New Research Developments

Prostate Cancer

• Based upon our prior work with fractionated dosing of our radiolabeled antibody 177Lu-J591, we performed the world’s first phase 1 dose-escalation trial of 177Lu-PSMA-617 without finding any dose-limiting toxicity (no major side effects despite higher and higher doses), presenting the initial results at the European Society for Medical Oncology (ESMO) 2018 Congress. The phase II portion of the trial is ongoing. We are also leading the first trial combining two different targeting agents (J591 and PSMA-617) designed to deliver more radiation to tumors and less to other organs.

•  Alpha particles are several thousand-fold more potent than beta-emitters such as 177 Lu. We are completing the phase 1 dose-escalation portion of the world’s first-ever clinical trial utilizing a powerful alpha particle (225Ac) directed almost exclusively at prostate cancer cells by linking it with our J591 antibody, which avoids salivary glands.

• As prostate-specific membrane antigen (PSMA) targeting enters “prime time,” the United States Department of Defense (DOD) has recognized our significant contributions to this evolving field with a grant that will allow us to research optimal patient selection for PSMA-targeted radionuclide therapy and assess the treatment’s immune effects.

• Thanks to developing technology utilizing circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), we are able to draw information about a patient’s tumor via a simple blood test. In our findings published by the American Association for Cancer Research (AACR) Clinical Cancer Research journal, we analyzed the relationship between chemotherapy treatment and expression of androgen receptor (AR) variants in CTCs of men with metastatic prostate cancer.

• We led a phase II clinical trial through the Prostate Cancer Clinical Trials Consortium (PCCTC) and discovered that an aggressive subset of disease called neuroendocrine prostate cancer (NEPC) is driven by a gene with an associated target known as aurora kinase. Further investigation into targeting of the gene may help us to refine therapy for this difficult-to-treat patient population. Our findings were published as a cover story in Clinical Cancer Research. 

• Working with collaborators and funded by the Prostate Cancer Foundation (PCF), we have developed unique genomics sequencing methodology called PCF SELECT that allows us to identify actionable mutations in men with advanced prostate cancer.

Kidney Cancer

• The number of United States Food and Drug Administration (FDA)-approved drugs for patients with advanced kidney cancer continues to grow. Dr. Ana Molina leads our team in offering clinical trials focused on novel targeted agents, combination treatments, and risk-directed therapies for various subtypes of kidney cancer.

• Working together with the Englander Institute for Precision Medicine, we are evaluating genetic signatures from patient tumor specimens and developing organoids that can be used to test novel pathways and tailor treatment to each individual patient.

• Laboratory studies of our in vivo kidney cancer models have resulted in discoveries regarding the metabolism of the disease. Understanding the role of the mitochondria (a cell’s power generator) in kidney cancer is leading us to novel therapeutic approaches to block tumors from growing and spreading.

Bladder Cancer

• Five immune therapies are now FDA-approved for people with advanced bladder cancer. We continue research to improve upon these agents by combining them with targeted therapeutics with the potential to replace chemotherapy. Collaboration with EIPM will help us to identify tumors most likely to benefit from these treatments.

• Dr. Bishoy Faltas and his lab team are focused on understanding the role of a specific family of proteins that cause mutations (genetic errors) that may be the underlying cause of bladder cancer. This research will enable us to develop new treatments to target the newly-identified genes that drive the disease.

• Based upon Dr. Faltas’ prior high-impact Nature Genetics publication that identified the genetic mechanisms by which bladder cancers become resistant to chemotherapy and new drug targets, we are launching an innovative new clinical trial utilizing a targeted drug that inhibits bladder cancer growth, the first time this type of drug is being tested in bladder cancer.

• We are conducting clinical trials of two antibody-drug conjugates (sacituzumab govitecan and enfortumab vedotin) designed to deliver potent chemotherapy-like toxins preferentially to cancer cells. This type of therapy is anticipated to become one of the standard approaches to bladder cancer treatment.

Precision Medicine

• Using samples of patient tumors (drawn via needle biopsy), we can create small 3-D tumor representations known as organoids that mimic the way that cancer cells grow within the body and respond to treatment. Our team has worked to develop this exciting new form of precision medicine, which is especially significant for rare cancers with a lack of preclinical models available for study.

We are moving closer to our ultimate goal of curing genitourinary cancers and look forward to continued progress in the years ahead.

 

Bladder Cancer – From the Basics to State-of-the-Art

One of the many ways Weill Cornell Medicine and NewYork-Presbyterian provide supportive resources to the community is by offering physician-led presentations and Q&A sessions in the Myra Mahon Patient Resource Center.

Two weeks ago, Dr. Scott Tagawa, medical oncologist and Director of the Weill Cornell Medicine Genitourinary (GU) Oncology Program, presented to and educated people in the local community about bladder cancer. His presentation was titled, “Bladder Cancer: From the Basics to State-of-the-Art.” Following the presentation, all attendees were invited to ask Dr. Tagawa questions.

Key topics from Dr. Tagawa’s presentation included the most common risk factors for bladder cancer, different types of bladder cancer (also known as clinical phases), and corresponding treatment options, research, as well as the benefits of utilizing an individualized approach to treatment, also known as precision medicine.

Highlights from Dr. Tagawa’s presentation are outlined below.

Bladder Cancer Risk FactorsScreen Shot 2017-12-14 at 9.22.30 AM

Dr. Tagawa noted that anyone can be diagnosed with bladder cancer, however, factors such as age and exposure to cigarette smoke may increase the risk of bladder cancer from developing. Most people who are diagnosed with bladder cancer are older in age. In fact, the average age at diagnosis is 73. In addition, bladder cancer is twice as common among Caucasians as African Americans.

Clinical Phases of Bladder Cancer and Corresponding Treatment Options

BladderCancer_5Dr. Tagawa highlighted the importance of using a uniform method for developing and testing biomarkers in bladder cancer, a disease with a high incidence of recurrence and expensive clinical surveillance. He also pointed out that most bladder cancers are of a type called transitional cell, affecting the same kinds of cells (transitional cells) that are usually the cancerous cells responsible for renal pelvis, ureter as well as kidney cancers. Dr. Tagawa described the four main phases of bladder cancer.

Pre-Cancer Diagnosis

The first phase is to assess symptoms in high-risk individuals, which defines those who are likely to develop bladder cancer. The most common symptom of bladder cancer is blood in the urine and testing to include assessment for the possibility of cancer would be beneficial for a high-risk population. Risk factors include, those who are aged 65 years or older, have used tobacco and has family history of cancer.

Often, the first test in the assessment of a patient with the symptom of blood in urine (or reddish urine) is a urinalysis, which is a test to assess for the presence of blood versus other elements that may appear like blood in the urine.  Other tests may include the assessment of other urine or blood factors, including assessment for infection. One test that is more specific for bladder cancer is a urine cytology, which looks at the urine under a microscope to detect abnormal appearing cells. If these cells are seen, a cancer diagnosis may be made, as the bladder has “shed” these cells into the urine. However, this test does not detect all cases of bladder cancer. Physicians may also want to perform blood tests or scans including, CT scan, MRI and ultrasounds.

“Superficial” Non-Muscle Invasive Disease

Non-muscle invasive disease means the cancer is confined to the inner lining of the bladder with no evidence that it has spread to another part of the pelvis or other organs. It used to be referred to as “superficial” bladder cancer, but this term is confusing since this stage of cancer often does invade into the first lining of the bladder. This type of bladder cancer comprises about 70% of all cases of newly-diagnosed bladder cancer. These patients are typically managed with resection (surgical removal of the cancerous parts of the bladder using a scope/camera), sometimes followed by intravesical therapy (usually immunotherapy with bacillus calmette-guerin), a process where the physician inserts a liquid drug directly into the bladder through a catheter. The drug can affect the cells lining the bladder without having major effects in other parts of the body.

Muscle Invasive Disease

In patients with muscle invasive disease, the cancer has spread into the muscle wall of the bladder. Those with this type of bladder cancer, which comprise of approximately 40% of all bladder cancer patients, are preferentially treated with systemic neoadjuvant chemotherapy followed by surgery to remove the bladder. Dr. Tagawa explained the different types of surgery patients may undergo if they are diagnosed with muscle invasive disease. The first is transurethral bladder tumor resection (TURBT), in which the surgeon removes the tumor using a tool with a small wire loop. Another form of surgery is a radical cystectomy, the removal of the whole bladder and possibly nearby tissues and organs. In addition, lymph nodes in the pelvis area are removed for both men and women, also known as a pelvic lymph node dissection. A selected subgroup of patients may have similar outcomes with a combination of initial TURBT surgery followed by chemotherapy and radiation.

Metastatic Disease

Patients with metastatic bladder cancer, accounting for approximately 15% of bladder cancer patients, have cancer that has extended through the bladder wall and invaded the pelvic and/or abdominal wall. Dr. Tagawa noted that while the other clinical states are treatable, if someone is going to pass away from bladder cancer, they would most likely be at the metastatic disease state. Dr. Tagawa highlighted that chemotherapy with platinum-based regimens remains the mainstay of first-line treatment for metastatic disease. He explained that if physicians combine platinum-based chemotherapy (e.g. cisplatin) with other treatments, patients will most likely benefit from positive clinical outcomes, resulting in tumor shrinkage and longer overall survival rates.

Systemic immunotherapy (administered into veins as opposed to only instillation in the bladder) is another treatment approach and one in which bladder cancer patients tend to have positive responses. The type of immunotherapy drugs given to patients with bladder cancer are known as immune checkpoint inhibitors, as they “release the brakes” on the immune system and allow immune cells to attack tumors. The first Food and Drug Administration (FDA)- approved immunotherapy drugs is tecentriq, also known as atezolizumab, which is an immune checkpoint inhibitor that selectively binds to cancer cells based on the presence of PD-L1, a protein on the tumor’s surface.  There are now five such drugs approved for bladder cancer – more than for any other cancer type.

Treatment Approaches in the Pipeline

Dr. Tagawa noted that we’ve come a long way in recent years with the most available treatment options than ever before for bladder cancer patients. He emphasized, though, that there is still room for improvement with the development of more treatments and additional treatment combinations to increase survival rates for patients. One of the ways physicians are able to do this is by utilizing precision medicine, treating each patient as an individual based on his or her own genetic makeup. For bladder cancer patients, physicians look at the different genes and whether the genetic mutations are within the tumor, or germline, to determine the best treatment options. Some of the most promising drugs for bladder cancer work best in the presence of certain altered genes. Another way clinicians are able to continue utilizing precision medicine is through clinical trials, which pave the way toward further scientific advances that could potentially find a cure for bladder cancer, in addition to other cancers. Weill Cornell Medicine and NewYork-Presbyterian offer many bladder cancer-specific trials that you can search for here.

Overall, Dr. Tagawa reinforced the benefit of working with a multidisciplinary team, which should include at least a surgeon, radiation oncologist and medical oncologist. He concluded his talk by emphasizing how clinical research has progressed over the years and what it has taught us – “we have seen translational therapy lead to real clinically relevant improvement for patients.”

Watch Dr. Tagawa’s full presentation below.

Movember 2017 is Here!

For nearly 10 years, we have been proud to participate in a month-long campaign to raise awareness and funds for men’s health each November, also known as Movember.

The campaign dates back to 2003 when two friends in Australia tried to bring back the moustache trend by growing out moustaches (or “mo’s” as they are commonly called in Australia) during the month of November. The following year, after realizing that this facial hair served as a conversation-starter, they decided to channel that energy to raise money for prostate cancer research.

Awareness (and mustaches) have grown over the years, and in 2007, Movember officially launched a global campaign to change the face of men’s health – literally and figuratively through increased awareness and funds. Another way people can get involved is by “moving” and setting a walking, running, biking or swimming goal and working to achieve it every day throughout Movember. Today, over 5 million people from more than 20 countries have collectively raised over $700 million dollars. The Movember Foundation uses this money to fund research around the world to reduce the number of men dying from prostate and testicular cancer, as well as mental health issues. Movember is committed to funding research that will reduce the number of deaths from prostate and testicular cancer by 50% by 2030.

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From L to R: Dr. Scott Tagawa, last year’s Movember Captain, Dr. Daniel Margolis, this year’s Movember captain

We’ve been proud Movember partners for nearly 10 years now and have benefitted from many Movember research grants to further our cancer research, most recently being named one of six teams to receive a 2017 Challenge Award from the Prostate Cancer Foundation (PCF) and the Movember Foundation to investigate new, cutting-edge treatments for metastatic prostate cancer.

This 2017 Movember-PCF Challenge Grant has funded our latest research developing new treatments for treatment-resistant advanced prostate cancer. More details on the grant and research it supports can be found here.
In past years, Movember-funded grants have supported our research in the following areas:

  • Blood tests that assess the tumor’s circulating DNA to predict reasons for treatment resistance.
  • Circulating tumor cell (CTC) tests to predict which patients are more or less likely to respond to hormonal therapy or chemotherapy.
  • Assessing the genome of initial tumors in the prostate compared to advanced, treatment resistant tumors.
  • Evaluating inflammation in adipose (fat) tissue around the prostate, which is associated with tumor growth.

Throughout the month of November, staff and physicians at Weill Cornell Medicine and NewYork-Presbyterian will be growing mustaches, exercising and raising funds for the Movember Foundation in support of our shared mission to cure cancer.

Get Involved!

  • Join our team by visiting https://moteam.co/wild-weill-cornell-mos
  • Grow a moustache and commit to going razor-free. It’s a great conversation starter to encourage friends and family members to donate to Movember.
  • Spin for a cure! Kill two birds with one stone. Get your workout in and support the Wild Weill Cornell Mos. Attend our cycling events on November 16th and 18th, with proceeds benefiting our team’s Movember fundraising goal.
  • Shave the date and celebrate the end of Movember by attending a happy hour. Stay tuned for final details including date and location.

Last year, we raised $13,000. We want to top that this year by raising $20K or more. Help us get there and remember that every dollar counts in the quest to cure cancer!