Author Interviews, Cancer Research, Chemotherapy, Melanoma, NYU / 27.06.2025
NYU Study Finds Genetic Mitochondrial Trait Confers Resistance to Checkpoint Inhibitors in Melanoma
MedicalResearch.com Interview with:
[caption id="attachment_69251" align="alignleft" width="156"]
Dr. Kirchhoff[/caption]
Tomas Kirchhoff, PhD (corresponding author)
Associate ProfessorLaura and Isaac Perlmutter Cancer Center
New York University School of Medicine
Robert Ferguson PhD
Senior Scientist at NYU Langone Medical Center
Kelsey Monson, PhD
Immuno-Oncology Postdoctoral Researcher
Icahn School of Medicine at Mount Sinai
MedicalResearch.com: What is the background for this study? Would you briefly explain how mitochondrial DNA differs from chromosomal DNA?
TK: Immune checkpoint blockade has changed the way we treat several cancers, including advanced melanoma. Before these therapies, the treatment options were very limited, but now more than half of patients experience significant tumor shrinkage or disease control.
KRM: Despite these advances, many patients still do not respond to treatment. One of the main challenges in cancer medicine today is to find ways to predict which patients will benefit from these therapies before treatment begins. This approach is key to personalizing care and improving outcomes.
RF: Mitochondria are small structures inside our cells that produce the energy needed for cells to function. Unlike most of our DNA, mitochondrial DNA is inherited only from the mother. Scientists can categorize this mitochondrial DNA into groups called haplogroups, based on unique variations in the genetic code. These haplogroups can provide insight into how cells produce energy and may affect a person’s health or response to cancer treatment.
Dr. Kirchhoff[/caption]
Tomas Kirchhoff, PhD (corresponding author)
Associate ProfessorLaura and Isaac Perlmutter Cancer Center
New York University School of Medicine
Robert Ferguson PhD
Senior Scientist at NYU Langone Medical Center
Kelsey Monson, PhD
Immuno-Oncology Postdoctoral Researcher
Icahn School of Medicine at Mount Sinai
MedicalResearch.com: What is the background for this study? Would you briefly explain how mitochondrial DNA differs from chromosomal DNA?
TK: Immune checkpoint blockade has changed the way we treat several cancers, including advanced melanoma. Before these therapies, the treatment options were very limited, but now more than half of patients experience significant tumor shrinkage or disease control.
KRM: Despite these advances, many patients still do not respond to treatment. One of the main challenges in cancer medicine today is to find ways to predict which patients will benefit from these therapies before treatment begins. This approach is key to personalizing care and improving outcomes.
RF: Mitochondria are small structures inside our cells that produce the energy needed for cells to function. Unlike most of our DNA, mitochondrial DNA is inherited only from the mother. Scientists can categorize this mitochondrial DNA into groups called haplogroups, based on unique variations in the genetic code. These haplogroups can provide insight into how cells produce energy and may affect a person’s health or response to cancer treatment.
Dr. Jerusalem[/caption]
Dr. Guy Jerusalem, MD, PhD
CHU Sart Tilman Liege and Liege University
Liege, Belgium
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: BOLERO-6 was conducted to fulfill postapproval regulatory commitments to the FDA and EMA to estimate treatment benefit with EVE + EXE vs EVE alone or CAP for ER+, HER2− ABC that had progressed on an NSAI. Everolimus plus exemestane has not previously been compared with everolimus alone or capecitabine in a randomized setting.Data describing everolimus alone are limited to a single phase 2 study of just 19 patients. Thus, the FDA deemed it important to ascertain the efficacy of everolimus alone for ER+ breast cancer, and to determine the contribution of exemestane to combination therapy with everolimus. Capecitabine is often the first chemotherapeutic agent given for ER+ breast cancer that has progressed on anti-estrogen therapy. It has a reported PFS of 4.1–7.9 months among patients with HER2-negative advanced breast cancer. However, it has a different safety profile to everolimus or exemestane, and a comparison of endocrine-based combination therapy with single-agent chemotherapy was yet to be conducted.
The median PFS with EVE + EXE (8.4 months) was consistent with BOLERO-2 (7.8 months), and compared to EVE alone here (6.8 months) corresponded to an estimated 26% reduction of risk of disease progression or death (HR 0.74).
A numerical median PFS difference was observed for CAP over EVE + EXE (9.6 vs 8.4 months), which may be attributed to various baseline characteristics favoring CAP and potential informative censoring. The median PFS with capacitabine was longer than expected based on previous trials. Interpretation of the results of BOLERO-6 must consider the limited sample size and open-label design. 











