�Research for Her Future
Finding paves way for ovarian cancer trials
Ovarian cancer is the deadliest of the reproductive cancers, attacking grandmothers, mothers and even their daughters.
Typically ovarian cancers strike postmenopausal women, but one very rare form — small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) — targets young women and girls, killing two-thirds of these patients within two years.
“I am a young scientist, age 30, and these women are even younger than I am,” said Dr. Jessica Lang, a postdoctoral fellow in Dr. Will Hendricks’ Lab in the Integrated Cancer Genomics Division at TGen. “They may have kids of their own — they may be kids themselves. Because this is a reproductive cancer, they may never have the ability to bear children, if they do survive this cancer at all.”
Dr. Lang’s research has taken on special meaning this year as she anticipates the birth of her first child — a daughter.
“These women receive their diagnosis when they are in the prime of their lives: launching their careers, starting their families and exploring the world,” she said. “We want to find effective treatments for these young women that will give them hope to live a long life — or even to have a fighting chance.”
Now, there is hope: The results of a study published earlier this year by TGen researchers in the journal Clinical Cancer Research suggest an existing leukemia drug, ponatinib, shows promise against SCCOHT. Dr. Lang was co-lead author on the study with Dr. Hendricks.
Additionally, Dr. Sunil Sharma, TGen’s Deputy Director of Clinical Sciences and Director of Applied Cancer Research and Drug Discovery, helped develop a drug, seclidemstat, at Salarius Pharmaceuticals of Houston that also shows promise against SCCOHT.
From discovery of the driver for this cancer to development of a possible treatment, TGen has been leading the charge against SCCOHT.
In 2014, TGen led an international team that identified a mutation in the SMARCA4 gene that causes SCCOHT. The American Society of Clinical Oncology recognized the discovery as one of the year’s biggest cancer research breakthroughs in its publication, Clinical Care Advances 2015.
Now, we are on the verge of testing these promising treatments in clinical trials, thanks to the leadership of Colleen’s Dream Foundation, an Arizona-based nonprofit founded by Nicole Cundiff and her husband Billy, a 12-year veteran kicker in the NFL.
Colleen’s Dream Foundation was honored with 2018 TGen Collaborative Spirit Award for its commitment to ovarian cancer research. Colleen’s Dream recently awarded TGen $450,000 to fund a clinical trial for these new ovarian cancer treatments.
“The research being done at TGen is some of the most exciting we’ve ever seen,” said Nicole Cundiff, CEO of Colleen’s Dream Foundation. “Whether the drug they developed leads to another amazing discovery, or it becomes a first line ovarian cancer treatment, we truly believe what they’re doing will move the needle and we couldn’t be more proud to support an institute located here in Arizona.”
Two Shots at SCCOHT
SCCOHT is interesting because it is driven by a single genetic mutation (in SMARCA4), whereas most cancers have mutations in many genes that contribute to tumor development.
With a single genetic mutation, SCCOHT is relatively simple to study. It becomes more tantalizing because the genetic mutation that drives SCCOHT is found in a complex of proteins called SWI/SNF, which is mutated in one-fifth of all cancers.
“If we can understand how this (SWI/SNF) affects this rare ovarian cancer, we can translate these same findings to a large number of other cancer types, including other forms of ovarian cancer, lung cancers, pancreatic cancers and others,” Dr. Jessica Lang explained.
SWI/SNF is a protein complex that regulates the chromatin environment, or the way DNA in the cell is packaged so that some genes are expressed and others are not. The TGen team is trying to identify how the loss of the chromatin regulator SWI/SNF impacts the development of cancer.
SMARCA4 is known as an “epigenetic” gene that broadly controls how other genes are regulated in the genome. When SMARCA4 is mutated, it is broken and cancer can develop through sweeping epigenetic imbalances. Seclidemstat has shown promising preclinical results in ovarian cancers and is also currently being clinically evaluated in other cancers.
Thus, we have two shots to take down SCCOHT.