The SU2C Breast Cancer Dream team showed that a drug (palociclib) for advanced breast cancer dramatically increased survival, gaining “breakthrough therapy” status from the FDA — reserved for important and essential therapies that may demonstrate substantial benefits to patients.This approval is intended for postmenopausal women with estrogen receptor (ER–positive, human epidermal growth factor receptor 2 (HER2–negative metastatic breast cancer who have not yet received an endocrine-based therapy. It is to be used in combination with letrozole, another FDA-approved product used to treat certain kinds of breast cancer in postmenopausal women. This approval was a first-in-class CDK4/6 inhibitor approval by the FDA. It improved treatment options for women with metastatic disease.

A new combination of drugs that lengthens lifespan in advanced pancreatic cancer was approved by the FDA, based on work by the SU2C Pancreatic Cancer Dream Team. This was the first approval for a first-line pancreatic cancer treatment in 15 years. This combination has become first-line, standard of care for many pancreatic cancer patients across the US.

In December 2016, the FDA granted accelerated approval to a new drug, rucaparib (or Rubraca from Clovis Oncology to treat women with BRCA1/2 mutated ovarian cancer, making it only the second PARP inhibitor to gain approval. The approval was based in part on data from a study conducted by the SU2C Ovarian Cancer Research Alliance–National Ovarian Cancer Coalition Ovarian Cancer Dream Team,among others. This treatment is for women

• whose disease has progressed despite multiple rounds of platinum-based chemotherapy.

Research by the SU2C-St. Baldrick’s Pediatric Cancer Dream Teamsupported FDA approval of two new treatments for Acute Lymphoblastic Leukemia in children and young adults. This first -of-its kind therapy trains patients’ immune cells to eliminate cancer. These two related FDA approvals include the chimeric antigen receptor T-cell (CAR T-cell) therapy Kymriah™ (tisagenlecleucel, from Novartis, which was approved by the FDA in September 2017for the treatment of relapsed or difficult-to-treat leukemia in children and young adults. Scientists on this Pediatric Dream Team helped carry out the preliminary clinical work that led to the conclusive trial for this first-of-its-kind therapy that trains a patient’s immune cells to eliminate cancer. The FDA also approved a new treatment to manage severe cytokine release syndrome (CRS), the “cytokine storm” that affects some patients. SU2C-supported scientists identified biomarkers that can help predict which patients receiving T-cell therapy will encounter CRS. The biomarkers will help guide management of the patient and mitigate the effects of CRS.

SU2C-Prostate Cancer Foundation Prostate Cancer Dream Team researchers have identified precision or personalized strategies to treat men with metastatic cancer with a novel combination of existing DNA Repair drugs for men with advance prostate cancer who have developed BRCA1/BRCA2 mutations.  This novel combination of existing drugs was awarded FDA Breakthrough Therapy Designation in 2016 to fill an unmet need in prostate cancer. The Dream Team determined that men with advanced prostate cancer are more likely to have actionable genetic mutations than men whose prostate cancer is localized. Therefore, men with metastatic prostate cancer should have their DNA sequenced to see if they are candidates for targeted therapies such as DNA-repair, PARP inhibitor drugs.

TheSU2C Pancreatic Cancer Dream Team developed a new method of identifying pancreatic tumors that have spread to the brain and liver, which could significantly aid in diagnosis.

• The Pancreatic Cancer Dream Team discovered that these cancer cells might be tricked into “eating” a cancer-killing drug.

The SU2C Epigenetics Dream Teamshowed that epigenetic therapy makes lung cancers more vulnerable to further treatment. It’s a new way of thinking about treatment that could change the way we treat other cancers. The Epigenetics Dream Team quickly moved a new leukemia drug into trials in patients. Follow-up trials are very promising.

The SU2C-CRI Immunology Dream Team harnesses patients’ own immune systems to attack cancer, an exciting new direction in research. Melanoma cells, like most cancer cells, are able to impersonate normal cells and therefore are not identified by the body’s immune system. Melanoma cells with a BRAF gene mutation are also able to turn off the immune system’s response and keep growing. Once it starts spreading, melanoma acts aggressively and can often move to the brain. Science does not yet have treatments for many mutations that drive melanoma. To get around this lack of treatments, SU2C researchers are focused on both helping the immune system recognize melanoma cancer cells and stopping those cells from turning off the immune system. In doing so, they have developed a treatment that, for the first time, administers two types of immunotherapy simultaneously to control cancer. First, adoptive cell therapy teaches the immune system to recognize the cancer cells as a foreign invader, but the cancer can quickly adapt itself to avoid detection. The addition of a second immunotherapy, called IPI (for ipilimumab, uses antibodies to block the action of protein receptors that can stop the immune system’s work. The combined effects of the two therapies seem to be enough to eliminate the cancer. Further testing of the concept is being supported by SU2C. In addition to these advances in treating melanoma, studies by the Dream Team show encouraging effects in advanced lung cancers and additional clinical trials are underway investigating immunotherapies potential in bladder cancers.

SU2C researchers have significantly advanced the use of Organoids as an effective tool to identify targeted and personalized treatment for individual patient’s cancer. Scientists and medical doctors both, for different reasons, need to be able to grow cancers in laboratory settings to test new therapies and determine which drugs might work best for a particular patient. Recent breakthroughs in isolating diseased cells and growing them in the lab is making this possible, and SU2C has been at the forefront of bringing the new technology to the study and treatment of cancer. Organoids are miniature cellular systems, created from a person’s own tissues, that allow scientists to understand and study disease progression in a realistic setting. This allows scientists to quickly observe how new treatments affect not only the tumor cells, but also the surrounding tissue that supports cancer growth. This powerful system more closely mimics the real-life situation, avoiding the false positives and other pitfalls associated with animal tissue samples or other laboratory techniques. Organoids can be used to test targeted therapies, combinations of drugs, and methods for detecting cancers in humans. SU2C grantees are working to make this possible in breast, colon, pancreatic, esophageal and ovarian cancers.

SU2C researchers are imaging cancer to see how cells “eat” sugars to shed light on cancer progresses and how to detect cancer. In order to perform their work and to replicate, most cells in the body rely on glucose as their primary energy source, but there are a number of other sugars and amino acids that circulate in the bloodstream for cells to ingest for fuel. Some tumors use glutamine as their energy source, which offers scientists an intriguing new way to see and measure the progress of cancer cells once they have been located. SU2C-supported researchers have created a “tagged” dye version of glutamine that can be seen on scanners after a cell absorbs it. This provides for better imaging of tumors. As a result, some cancers that are notoriously difficult to measure can receive a detailed confirmatory diagnostic, for instance when a patient is being investigated for possible pancreatic cancer after an MRI shows a shadow on the pancreas. Originally developed for better imaging of pancreatic cancers, the technique also shows promise in measuring and monitoring the progress of some brain cancers. If the technology can be developed for widespread use, it will allow doctors to detect the spread of cancers in the body, measure responses to treatment, determine when new medicines are needed, and reduce the reliance on expensive and complicated PET scanning for patients with cancer.

Working with pharmaceutical companies, the SU2C Women’s Cancers (PI3K) Dream Teamlaunched clinical trials of a new combination therapy aimed at a common “signaling network” in cancer cells. Currently, doctors lack effective treatment options for the subtype of breast cancers known as “triple negative” breast cancer, which accounts for about 20% of new breast cancer diagnoses each year. Starting in 2015, SU2C-funded scientists have tested a new combination of experimental treatments for these cancers. The combination involves a PARP inhibitor which turns off one of the cell’s DNA-repair mechanisms and helps halt future growth of the cancerous cell. The second agent is PI3K inhibitor, which shuts down a kinase that broadly stimulates cell growth. Together, a dramatic synergistic response has been observed, and scientists are working to understand why. It seems that the PI3K inhibitor makes the cells more sensitive to the PARP inhibitor. Clinical trials to further refine this discovery are underway, and later in 2019 we will know if a new treatment can be widely tested for triple-negative breast cancer. The combination was effective in certain patients with a particular subtype of breast cancer.

The SU2C Circulating Tumor Cell (CTC) Chip Dream Teamdeveloped a device that can find a single cancer cell amid 1 billion cells in a teaspoon of blood and will allow doctors to monitor and fine-tune treatments in cancer patients in real time.

The SU2C-Melanoma Research Alliance Dream Teamreceived the first-ever FDA approval for a new approach to rapid genetic profiling of melanoma, which makes it possible to  match drugs to individual tumors based on their genetic characteristics –an example of “precision” or “personalized” medicine.