Jan Rosenbaum ’78

Hide and Seek: Targeting Treatment-Evading Cancer Cells

By
April Reese

Certain cancer cells can be masters of evasion. In some patients, they learn to sidestep chemotherapy drugs and other treatments. Jan Rosenbaum ’78, has dedicated her career to outsmarting these types of evasive cancer cells.

The startup she founded in 2020, Kurome Therapeutics, is developing novel therapies that disrupt the mechanism that allows blood cancer cells to grow and proliferate. The company’s work focuses on improving outcomes for patients with myelodysplastic syndrome (MDS), a blood cancer that often leads to acute myeloid leukemia (AML), and those with AML, a disease that is often a death sentence.

“We lose 50% of AML patients every year, and it’s because of resistance [of cancer cells to treatment],” Rosenbaum says. Eventually, the company hopes to develop treatments for other blood cancers as well, she adds.

Rosenbaum, who holds a doctorate in pharmaceutical chemistry, served as chief executive officer and chief scientific officer of Kurome Therapeutics until May 2025, when she stepped down after a merger with Disc Medicine. She continues to work for the company as a consultant.

The company is developing a therapy that targets signaling pathways involved in the dysregulated immune cell signaling that is co-opted by the cancer cells, allowing the cancer cells to survive. Kurome’s therapy targets three critical signaling proteins in blood cancer: IRAK1, IRAK4 and FLT3. These proteins tell the cell when to grow or divide as immature blood cells or to go on to become fully functioning mature blood cells. In a healthy person, FLT3 signals are carefully controlled, but in AML patients, they have mutated to override these checks and balances, allowing cell growth to spiral and develop into cancer. During treatment, FLT3 can evolve and mutate to resist therapy.

Similarly, in healthy immune cells, levels of IRAK1 and IRAK4 are low, but in blood cancer and in response to various therapies, they are elevated. Overactive IRAK signaling prevents the blood cancer cells from becoming fully functional mature blood cells.

Kurome Therapeutics is working to identify inhibitors that can keep FLT3 and IRAK1 and 4 in check, thereby disrupting cancer cells’ ability to circumvent chemotherapy.

“The cancer cell has lost one of its defense mechanisms,” Rosenbaum says.

Rosenbaum recently underwent treatment for multiple myeloma, an experience that gave her a deeper understanding of why the treatments she is helping to develop are needed.

“I’ve been able to use my knowledge from working in blood cancer to influence my own treatment. That’s been very, very helpful,” she says, adding that her cancer, which develops in plasma cells, was caught early. “And I’ve been able to use my experience as a patient to influence how we design our trial.”

For example, while having more data from bone marrow biopsies would be useful, knowing what it’s like to undergo a biopsy has helped her understand why that isn’t realistic. “Now I know how painful it is and why you can’t do a lot of bone marrow biopsies,” she says.

As Rosenbaum progresses through her own treatment, she continues to work with Kurome to help solve the resistance challenge. Clinical trials to test the company’s new resistance inhibitor drug will begin soon, she says. She’s hopeful that MDS and AML patients will have a better chance at beating their grim odds.

“We’re learning more and more about the mechanisms of resistance and the opportunities for intervention.”