New treatment identified for peripheral nerve sheath tumors

New Hope for Patients Facing Aggressive Nerve Tumor

Imagine a tumor not confined to bones or organs, but nestled within the intricate network of nerves. This is the reality for individuals diagnosed with malignant peripheral nerve sheath tumors (MPNSTs), a rare adn aggressive form of sarcoma with a high risk of spreading.

while MPNSTs can occur in the general population, they are also frequently associated with Neurofibromatosis type 1 (NF1), a genetic disorder that considerably increases an individual’s lifetime risk of developing these tumors.

Thankfully, a new ray of hope has emerged from research. A dedicated team of scientists at the Bellvitge Biomedical Research Institute (IDIBELL), the Germans Trias i Pujol Research Institute (IGTP), and collaborating institutions have made critically important strides in understanding and potentially treating this challenging disease.

For years,MPNST treatment has primarily involved surgery,with conventional chemotherapy and radiation therapy proving largely ineffective. This lack of viable options highlighted the urgent need for alternative therapies, prompting a collaborative effort to develop a powerful preclinical platform.

“It has been a patient and long collaborative work of many years that is now at its maturity. We are very happy that the platform has been a prosperous investment that is providing now all its potential,” said Dr. Conxi Lázaro, a senior author of the study. Dr. Lázaro and her team, alongside Dr. Eduard Serra and others, dedicated nearly 15 years to establishing patient-derived xenografts (PDX) of human MPNSTs, grown in immunodeficient mice. They also created multiple MPNST cell lines, forming a valuable resource for precision medicine approaches.

“I would like to thank many people involved, especially Dr.Juana Fernandez, who directs the Mouse Lab platform at IDIBELL. That has been key for this success,” dr. Lázaro added. The team also expressed gratitude for the unwavering support of the Fundación Proyecto Neurofibromatosis, emphasizing their invaluable contribution to this groundbreaking work.

This cutting-edge platform has allowed researchers to delve into the genetic underpinnings of MPNSTs, uncovering key mutations driving tumor growth. “The most common type of MPNSTs initiate by losing the function of three crucial genes,” Dr. Sara Ortega, lead author of the study, explains.

By understanding these vulnerabilities, researchers could begin to develop targeted therapies.

Building on this knowledge, the team focused on developing a novel three-drug combination therapy. “We combined a MEK inhibitor,
a BET inhibitor,and a CDK inhibitor,” Dr. Ortega continues.“this combination targets specific vulnerabilities of MPNSTs associated with the loss of PRC2 function, which plays a crucial role in regulating gene expression.”

Their initial findings in preclinical models were promising, with the three-drug combination showing significant antitumor activity, halting tumor growth and even causing tumor regression.

The team is now actively working to translate these findings into clinical trials, bringing this potential new hope for MPNST patients one step closer to reality.

“Our goal is to bring this treatment to patients quickly,” Dr. Ortega says. “This is a very promising development, and we are excited to see what the future holds.”

A 3-Drug Combo offers Hope for Children Battling Aggressive Cancer

There’s a glimmer of hope in the fight against malignant peripheral nerve sheath tumors (MPNSTs),a rare and aggressive cancer primarily affecting children and young adults. A groundbreaking new triple-drug therapy has shown remarkable results in preclinical studies, shrinking tumors and even leading to complete tumor disappearance in certain specific cases.

MPNSTs are notoriously difficult to treat, frequently enough stemming from genetic mutations in the NF1 gene, which plays a vital role in cell growth and division.This new research, lead by a team at the Germans Trias i Pujol Research Institute, focuses on targeting a specific vulnerability in MPNST cells linked to the loss of PRC2 function.

After painstaking laboratory testing, the researchers pinpointed the most effective drug combinations. These were then tested in a preclinical “humanized” model, utilizing patient-derived tumor samples implanted in mice. The results were overwhelmingly positive. While combinations of MEK and BET inhibitors showed promise, the triple combination of MEK, BET, and CDK inhibitors (MEKi-BETi-CDKi) delivered the most dramatic tumor reduction.

“we were thrilled with the combined MEKi-BETi treatment, seeing for the first time in our PDX models how human MPNSTs were shrinking,” shared Sara Ortega, lead author of the study and a key researcher on the project.”But the most incredible moment was witnessing some tumors completely disappear with the triple MEKi-BETi-CDKi combination. After all the hard work, seeing the potential clinical applicability was incredibly rewarding,”

The team’s success didn’t end in the lab.Close collaboration with pediatric oncologists, notably Dr.Héctor Salvador from Hospital Sant Joan de Déu, paved the way for translating these preclinical findings into actual patient care.The researchers’ work ultimately helped secure compassionate use approval for the MEKi-BETi combination in pediatric MPNST patients. Dr. salvador, alongside Dr. Claudia valverde from Vall d’Hebron Hospital, facilitated access to new inhibitors currently undergoing clinical trials. Furthermore, Dr. Salvador and Alicia Castañeda have begun administering the MEKi-BETi combination as compassionate use therapy for children battling MPNSTs.

New Hope for Aggressive Nerve Tumor: An Interview with Lead Researcher Dr.Sara Ortega

Malignant peripheral nerve sheath tumors (MPNSTs) are rare and aggressive cancers that often strike young people.A groundbreaking study conducted at the Germans Trias i Pujol Research Institute has provided a beacon of hope for patients battling this challenging disease.

“It’s been an remarkable journey, truly a team effort,” says Dr. Sara Ortega, lead author of the study. MPNSTs are frequently linked to genetic mutations in the NF1 gene, making them notoriously difficult to treat.Dr. Ortega’s team focused on pinpointing a specific vulnerability in these tumors associated with a loss of PRC2 function.Through extensive laboratory work, they discovered a powerful three-drug combination – involving MEK, BET, and CDK inhibitors (MEKi-BETi-CDKi) – that offered a promising new avenue for treatment.

“We tested these drug combinations in patient-derived tumor samples implanted in mice,” Dr. ortega explains. “The MEKi-BETi combination showed good tumor reduction, but the MEKi-BETi-CDKi combo delivered the most significant results, even causing complete disappearance of tumors in certain specific cases. It was truly remarkable to see.”

This preclinical success has directly translated into benefits for patients. Collaborative efforts with pediatric oncologists, particularly Dr. Hector Salvador from Hospital Sant Joan de Déu, have been instrumental in bringing this treatment to those in need.

“Our collaboration with pediatric oncologists, particularly Dr. Héctor Salvador from Hospital Sant Joan de Déu, has been crucial,” Dr.Ortega shares. “Their expertise helped us secure compassionate use approval for the MEKi-BETi combination in children with MPNSTs. Dr. salvador and his team, along with Dr. Claudia Valverde from Vall d’Hebron hospital, are now administering this treatment to young patients.”

While further research is needed to refine the management regimen and minimize potential side effects of the MEKi-beti-CDKi combination, the research team remains optimistic. “There is still a lot to do – further preclinical data, optimized treatment regimens, reduced toxicity – but the first steps for precision medicine in treating MPNSTs in the future are already in place,” concludes the research team.

This breakthrough offers a powerful example of how science, collaboration, and unwavering dedication can bring hope to those facing seemingly insurmountable challenges.

A Beacon of Hope: Advancing Treatment for MPNST

Recent breakthroughs in MPNST research offer a glimmer of hope for patients and their families. Dr. Ortega, a leading researcher in the field, shared insights into the promising future of MPNST treatment.

“More preclinical studies are needed to refine the treatment regimen and minimize potential side effects of the MEKi-BETi-CDKi combination,” Dr. Ortega explained.”However, the encouraging data and ongoing clinical trials in the USA provide a strong foundation for future clinical submissions. It’s a promising time for patients with MPNSTs, and we remain dedicated to advancing precision medicine for their benefit.

”

These words offer a powerful message to those battling this challenging disease. While research continues, progress is being made. Dr. Ortega emphasizes that hope remains a guiding light:

“Hold onto hope,” Dr.Ortega urges families facing the MPNST challenge. “The field of MPNST research is advancing rapidly, and we remain committed to finding better treatments and ultimately cures for this disease.”

These advancements highlight the importance of continued research and collaboration within the medical community. MPNST patients and their families can find solace in knowing that dedicated researchers are tirelessly working towards a brighter future.

What specific vulnerabilities in MPNSTs associated with a loss of PRC2 function were targeted by Dr. Ortega’s team?

New Hope for Aggressive Nerve Tumor: an Interview with Lead Researcher Dr.Sara Ortega

Malignant peripheral nerve sheath tumors (MPNSTs) are rare and aggressive cancers that frequently enough strike young people.A groundbreaking study conducted at the Germans Trias i Pujol Research Institute has provided a beacon of hope for patients battling this challenging disease.

Interview with Dr. Sara Ortega

“It’s been an remarkable journey, truly a team effort,” says Dr. Sara Ortega,lead author of the study. MPNSTs are frequently linked to genetic mutations in the NF1 gene, making them notoriously difficult to treat.Dr. Ortega’s team focused on pinpointing a specific vulnerability in thes tumors associated with a loss of PRC2 function.Through extensive laboratory work, they discovered a powerful three-drug combination – involving MEK, BET, and CDK inhibitors (MEKi-BETi-CDKi) – that offered a promising new avenue for treatment.

What makes this new three-drug combination so promising for treating MPNSTs?

“We tested these drug combinations in patient-derived tumor samples implanted in mice,” Dr. Ortega explains. “The MEKi-BETi combination showed good tumor reduction,but the MEKi-BETi-CDKi combo delivered the most meaningful results,even causing complete disappearance of tumors in certain specific cases. It was truly remarkable to see.”

How has this preclinical success translated into benefits for patients?

“Our collaboration with pediatric oncologists, especially Dr. Héctor Salvador from Hospital Sant Joan de Déu, has been crucial,” Dr.Ortega shares. “Their expertise helped us secure compassionate use approval for the MEKi-BETi combination in children with MPNSTs. Dr. salvador and his team, along with Dr.Claudia Valverde from Vall d’Hebron hospital, are now administering this treatment to young patients.”

What are the next steps in research and development for this promising treatment?

“More preclinical studies are needed to refine the treatment regimen and minimize potential side effects of the MEKi-BETi-CDKi combination,” Dr. Ortega explained.”However, the encouraging data and ongoing clinical trials in the USA provide a strong foundation for future clinical submissions. It’s a promising time for patients with MPNSTs, and we remain committed to advancing precision medicine for their benefit.

For families facing the MPNST challenge, what message of hope would you like to share?

“Hold onto hope,” Dr.Ortega urges families facing the MPNST challenge. “The field of MPNST research is advancing rapidly, and we remain committed to finding better treatments and ultimately cures for this disease.”