Ponatinib Shows Promise for Rare Ovarian Cancer Type that Affects Young Women

Thursday, March 08, 2018
Ponatinib (Iclusig), a drug that is used to treat leukemia, may also have potential in treating small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), according to a study published in Clinical Cancer Research. SSCCOHT is extremely rare, and mostly affects young women.

While most ovarian cancers are diagnosed after menopause at an average age of 63 years, according to the American Cancer Society, the average age of SCCHOT diagnosis is 24 years old. It has been diagnosed in babies as young as 14 months old. Traditionally treated with surgery and/or chemotherapy, SCCHOT has a 2-year survival rate under 35%, according to the University of Texas MD Anderson Cancer Center.

Researchers found that ponatinib, which is currently approved to treat chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) subtypes, delayed tumor growth and reduced tumor volumes in 2 patient-derived xenograft models and 1 cell line xenograft model by as much as 58.6%.

"Current treatment for this devastating cancer has such poor response rates and extreme toxicity that we must find better therapeutics," lead author Jeffrey Trent, PhD, FACMG, president and research director of the Translational Genomics Research Institute (TGen), said in a press release. "Our work identifies a new treatment strategy that could provide these young women with improved benefit."

SCCOHT formation and growth is driven by a genetic mutation that turns off the SMRCA4 gene, which was previously associated with lung, brain, and pancreatic cancers, researchers found. These tumors rely on receptor tyrosine kinase (RTK) cellular pathways, which ponatinib blocks–explaining why this drug shows promise for this patient population.

"We identified Iclusig [ponatinib] as the most effective clinically approved RTK inhibitor," said Jessica Lang, PhD, TGen post-doctoral fellow and co-lead author on the study, in the release. "It holds the potential for rapidly improving outcomes for these young patients."

The researchers hope that their findings will lead to larger clinical investigations of the agent, and ultimately review by the Food and Drug Administration.

"Evaluation of a panel of selective RTK inhibitors highlighted ponatinib as the most potent tested agent in SCCOHT cell lines," co-lead author William Hendricks, PhD, assistant professor in TGen’s Integrated Cancer Genomics Division, said in the release. "Clinical investigation of this FDA-approved oncology drug is warranted in SCCOHT."

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