New research from Memorial Sloan Kettering Cancer Center (MSK) identifies a tumor-secreted protein that primes the lungs for metastasis; shows how a new drug combination improves survival in patients with advanced clear cell renal cell carcinoma; and finds a three-drug combination works in most patients newly diagnosed with follicular lymphoma.
Tumor-secreted protein found to prime the lungs for metastasis
Lung metastasis is a leading cause of cancer-related death, yet the biological mechanisms that help tumors to infiltrate the lungs have not been well understood.
A new study from researchers at MSK and Weill Cornell Medicine has identified a protein called integrin alpha-5 as a key driver of lung metastasis across several cancer types — including melanoma, osteosarcoma, and colorectal cancer. The team found the protein paves the way for metastasis by making blood vessels leakier, allowing cancer cells to slip through and into lung tissue.
Tumors, the researchers found, release tiny molecular packages called extracellular vesicles and particles (EVPs), loaded with integrin alpha-5, that travel through the bloodstream to the lungs. Once there, the protein acts on macrophages — triggering the immune cells to release the inflammatory molecule IL-6, which in turn causes blood vessel walls to loosen, creating a path for circulating tumor cells to enter.
Notably, this effect was detectable within just one to two hours of EVP exposure — including in a breast cancer model that is not typically prone to lung metastasis. An analysis of human tumor data confirmed that high integrin alpha-5 expression is associated with poorer survival across several cancer types.
The findings open the door to potential clinical applications, the researchers note. Detecting integrin alpha-5-containing EVPs in the blood could help assess metastatic risk. Meanwhile, blocking the protein — particularly during surgery — may offer a new strategy to reduce the chance of metastasis.
MSK breast medical oncologist Jacqueline Bromberg, MD, PhD, and Weill Cornell Medicine pediatric oncologist David Lyden, MD, PhD, were co-corresponding authors on the paper.
Read more in Nature Cancer and in an accompanying article by Weill Cornell Medicine.
New drug combination improves survival in patients with advanced clear cell renal cell carcinoma
Patients with advanced clear cell renal cell carcinoma (ccRCC) are often first treated with immune checkpoint inhibitors, a type of immunotherapy, together with a targeted drug called a tyrosine kinase inhibitor (TKI). These drugs inhibit the growth and spread of tumors by preventing them from forming new blood vessels. While these treatments can be effective, not everyone’s cancer responds — and even cancers that do initially respond eventually show signs of progression. Researchers from MSK are working to find new treatments that can delay the cancer from worsening after first- or second-line treatment.
One promising option combines the TKI lenvatinib (Lenvima®) with belzutifan (Welireg®). Belzutifan is the first drug to target hypoxia-inducible factor 2α (HIF-2α), which is a protein that plays a central role in the growth and survival of clear cell RCC. Unlike TKIs, which primarily block signals that promote the growth of the blood vessels that feed tumors, belzutifan works through a different mechanism by blocking a tumor’s response to low-oxygen conditions.
Robert J. Motzer, MD, a genitourinary cancer specialist at MSK, and colleagues recently reported on the phase 3 LITESPARK-011 clinical trial. The study included patients whose disease had progressed after treatment with an immune checkpoint inhibitor. They were randomized to receive either belzutifan plus lenvatinib or cabozantinib (Cabometyx®), a standard TKI. Patients treated with the combination experienced longer progression-free survival than those receiving cabozantinib alone, with a median of 14.8 months compared with 10.7 months on the single drug.
“This is the first phase 3 trial of a HIF-2α inhibitor plus a VEGF-R-TKI, and the first phase 3 trial in RCC in the post immune checkpoint inhibitor setting to show improved outcomes versus a contemporary VEGFR-TKI, a setting of high unmet need,” Dr. Motzer says.
The findings from this trial suggest that combining drugs with complementary mechanisms may offer a new treatment option for patients whose disease progresses after immune checkpoint inhibitor treatment.
Read more in The Lancet.
Three-drug combination works in most patients newly diagnosed with follicular lymphoma
A three-drug combination that enables patients with follicular lymphoma to avoid chemotherapy is effective in almost all patients who have been newly diagnosed with the disease, according to a new study. The three drugs in the treatment are epcoritamab, rituximab, and lenalidomide.
The phase 1/2 clinical trial, called EPCORE NHL-2, enrolled 41 patients across the United States and Europe. After an average follow-up of almost three years, analysis showed:
- 95% of patients responded to treatment, and 88% achieved complete remission, meaning no detectable cancer remained.
- 90% still had no cancer at 33 months.
- None of the patients who responded required additional cancer treatment during the study period.
- Most side effects from the treatment were manageable, with low white blood cell counts being the most common.
Rituximab and lenalidomide are older cancer drugs that work on the patient’s immune system. Epcoritamab is a new form of immunotherapy that links cancer cells to the patient’s immune cells, making it easier for the immune system to destroy the cancer.
This same combination received approval from the U.S. Food and Drug administration in November 2025 for patients whose disease has come back after other treatments. That approval was based on trial led by lymphoma specialist Lorenzo Falchi, MD, of Memorial Sloan Kettering Cancer Center, who is also first author of the new study.
“Our study demonstrates that this chemotherapy-free combination produces deep and durable remissions for patients who are newly diagnosed with follicular lymphoma as well as those who have received other treatments,” Dr. Falchi says. “A larger phase 3 trial is currently underway to confirm these promising findings. This study will also look at whether treatment with a shorter course of epcoritamab will be as effective.”
Read more in Lancet Hematology.