image: An MSK researcher working in the lab.
Credit: Memorial Sloan Kettering Cancer Center
New research from Memorial Sloan Kettering Cancer Center (MSK) shows the Make-an-IMPACT program improves global access to genomic testing in pediatric cancer patients; helped develop an experimental antibody that shows promise against metastatic cancer; sheds light on the origins of ERG-driven prostate cancer; and finds Dupilumab is a successful agent to treat skin toxicities related to antibody-drug conjugates.
Make-an-IMPACT program improves global access to genomic testing in pediatric cancer patients
MSK-IMPACT®, a tumor test developed at MSK, uses information about cancer genomics to help determine the best treatment option for each individual patient. A new study looked at some of the benefits of MSK’s Make-an-IMPACT program, which provides no-cost MSK-IMPACT testing to patients being treated for rare cancers outside MSK.
This study focused on 63 pediatric patients enrolled in the program; 40% were located outside the United States. MSK-IMPACT was used to analyze either solid tumor tissue or cerebrospinal fluid in patients with cancers of the central nervous system (CNS).
The researchers, led by MSK Kids pediatric oncologist Neerav Shukla, MD, reported that testing results provided clinically relevant new diagnostic or prognostic information in 41% of patients with solid tumors and 38% of those with CNS tumors. Furthermore, several patients were able to receive targeted treatment based on test results. “This testing provides real-time diagnostic, prognostic, and therapeutic information to local physicians and their patients,” Dr. Shukla says. Read more in Clinical Cancer Research.
Experimental antibody shows promise against metastatic cancer
Researchers are optimistic after a small, first-in-human trial explored the safety and effectiveness of a novel treatment for several types of metastatic cancer using an engineered anti-CD40 antibody that is injected directly into the tumor. Metastasis is responsible for as many as 9 in 10 cancer deaths and remains a major priority for drug development.
Similar antibodies aim to activate the immune system by binding to the CD40 receptor and triggering a cascade of immune responses — this activation, however, can be too strong if given systemically, leading to widespread side-effects. This new antibody, called 2141-V11, was developed for local delivery, avoiding systemic toxicity. It was also designed to enhance binding to the FcγRIIB receptor, which acts as a scaffold to optimize CD40 activation within the tumor’s immune microenvironment.
The Phase 1 study included 12 patients with metastatic cancer, and found the treatment was well-tolerated, with no severe toxic reactions. Promisingly, two patients — one with breast cancer and one with melanoma — saw their tumors disappear, including injected tumors and distal, non-injected metastasis. Six additional patients saw their tumors shrink significantly. Experiments in mice further demonstrated the treatment’s effects. Promising results have prompted new Phase 2 studies at MSK in bladder and prostate cancers, as well as additional studies at other institutions.
“Our findings suggest that intratumoral administration of 2141-V11 is not only safe, but also an effective way to promote the immune interactions required to improve the body’s defenses against cancer,” says study co-first author Juan Osorio, MD, an oncologist and new lab leader in MSK’s Immuno-Oncology Program, and a recent member of the lab of senior study author Jeffrey Ravetch, MD, PhD, at The Rockefeller University. Read more in Cancer Cell.
Shedding light on the origins of ERG-driven prostate cancer
The laboratory of physician-scientist Charles Sawyers, MD, has made new insights into the origin of prostate cancers driven by the ERG transcription factor. Mutations in the ERG gene — specifically translocations — are a hallmark of prostate cancer. They cause overexpression of the ERG protein, leading to aberrant cellular behavior that can trigger cancer.
In mice, the researchers found tumor-causing ERG activity in subpopulations of basal cells that co-express luminal genes (BasalLum cells), rather than in the broader population of ERG+ luminal cells. When ERG is activated, the BasalLum cells generate highly proliferative intermediate cells, which have stem-like properties. The researchers conducted a single-cell analysis of human prostate cancer cells and found a correlation. In addition, the presence of these intermediate cells in patients is associated with a worse prognosis.
The study highlights the complexity of prostate cancer by identifying distinct subpopulations within tumors that can drive cancer initiation and growth. It underscores the power of analyzing single cells rather than bulk cell populations. The finding also could explain why certain treatments are ineffective and points to the need for targeted therapies against specific cell populations. Read more in Nature Genetics.
Dupilumab is a successful steroid-sparing agent to treat skin toxicities related to antibody-drug conjugates
Antibody-drug conjugates (ADCs) are a class of anticancer drugs that combine the power of chemotherapy with the precision of a targeted therapy. They increasingly are being used to treat a range of cancers. Despite targeting specific proteins, ADCs still have adverse effects on various organ systems. One of the most common is cutaneous (skin) toxicity, which can lead to dose reductions and treatment interruptions.
Researchers at MSK led by dermatologist Allison Gordon, MD, decided to look at whether the drug dupilumab (Dupixent®) would be effective in improving high-grade cutaneous toxicities seen with ADCs. Dupilumab is used to treat eczema and other diseases characterized by severe inflammation.
The team looked at medical records from 27 patients who had skin toxicity while on ADC therapy for cancer. Eleven patients were treated with dupilumab, while 16 were given systemic steroids. The researchers found that 73% of the patients treated with dupilumab had full resolution of skin toxicity; the remainder had partial response. Comparatively, only 56% of patients who took steroids saw a full response and 25% had some improvements in their skin. Nearly half of patients taking steroids had to discontinue them due to side effects; none who took dupilumab had to stop. Most importantly, dupilumab managed skin toxicity and enabled patients to continue with or resume their life-prolonging anticancer therapy.
“Dupilumab appears promising as a steroid-sparing treatment of ADC-induced cutaneous toxicities,” the study authors wrote. “Further research is essential to explore its broader utility and economic feasibility.” Read more in JAMA Dermatology.