Targeting ROR1 in Blood Cancers

If you or a loved one is navigating a blood cancer diagnosis, understanding how ROR1-targeted therapies work—and whether they could apply to your specific cancer type—can help you make more informed treatment decisions. 

Main points:

• ROR1 is a receptor found on the surface of cancer cells, rarely present in healthy adult cells, making it a promising treatment target for various blood cancers.
• Early studies show that therapies targeting ROR1—such as CAR T-cell therapy, monoclonal antibodies, and small molecule inhibitors—may be effective in certain blood cancers like CLL and MCL.
• Combining ROR1-targeted therapies with other treatments like venetoclax may help overcome drug resistance and improve patient outcomes.

In the sections below, continue reading to learn how these therapies are being tested, which blood cancers they may benefit most, and what early research is revealing about their potential to improve outcomes. 

What Is ROR1 and Why Does It Matter for Blood Cancer Patients?

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a protein that plays a role in early development. In adults, it's mostly inactive—but in several cancers, including chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), ROR1 is turned back on and helps cancer cells grow and survive.

Because healthy adult tissues show little to no ROR1 activity, therapies that target it are less likely to harm normal cells. This makes ROR1 an appealing focus for developing more precise cancer treatments with fewer side effects.

For other blood cancers like multiple myeloma, acute myeloid leukemia (AML), and large B-cell lymphoma (LBCL), researchers have found ROR1-positive cancer cells in some patients. Early lab studies suggest that targeting ROR1 might help, but more research is needed to know how well these treatments work in real-life settings. 

Clinical Trial Treatment Options That Target ROR1

Several types of therapies are being developed to block ROR1 and stop its cancer-supporting activity:

• Monoclonal antibodies like cirmtuzumab designed to attach to ROR1 on cancer cells and block its signals. Early trials show this approach may be effective when combined with other treatments like venetoclax, which targets another cancer-promoting protein, BCL-2.
• Small molecule inhibitors such as KAN0441571C are designed to enter cancer cells and shut down ROR1 from the inside. These are showing potential, especially in patients whose cancers resist standard therapies.
• Antibody-drug conjugates (ADCs) like zilovertamab vedotin deliver chemotherapy directly to ROR1-positive cells, limiting damage to healthy cells. Click here to access a recruiting clinical trial for relapsed/refractory CLL, MCL, and follicular lymphoma patients.
• CAR T-cell therapy that modifies a patient’s own immune cells to target ROR1-positive cancer cells. This approach is still in early testing.
• Bispecific antibodies engineered to bring T-cells into close contact with cancer cells that express ROR1, helping the immune system do its job more effectively.

Why Combination Therapies Could Be the Future

One of the biggest challenges in blood cancer treatment is drug resistance—when cancer stops responding to treatment. Studies suggest that using a combination of therapies that target different pathways can reduce the risk of resistance.

For example, combining anti-ROR1 therapies with venetoclax may work better than either alone. This is especially important for people with high-risk or relapsed disease.

Bottom Line

If you’re living with CLL, MCL, or another ROR1-positive blood cancer, the development of ROR1-targeted therapies could eventually offer more effective and less toxic treatment options. While many of these therapies are still in clinical trials, early results are promising and could lead to new standard-of-care treatments in the future.

As research continues, it’s important to stay informed about clinical trials and emerging therapies. Talk to your doctor about whether any new treatment options may be appropriate for your specific situation. 

Continue Exploring Advancements in Blood Cancer Treatments

Source: 

• Therapeutic advances in the targeting of ROR1 in hematological cancers