Oncotarget

BUFFALO, NY – July 1, 2025 – A new #review was #published in Volume 16 of Oncotarget on June 17, 2025, titled “Optimizing enfortumab vedotin plus pembrolizumab therapy.” First authors Elias Antoine Karam of the Gustave Roussy and Saint-Joseph University of Beirut and Yaghi César Céline from the Saint-Joseph University of Beirut, along with their colleagues, reviewed recent developments about treating advanced urothelial carcinoma (aUC), an aggressive form of bladder cancer. Their review highlights how combining enfortumab vedotin and pembrolizumab as a first-line treatment offers a major improvement for patients with limited options and poor prognoses. Advanced urothelial cancer has traditionally been treated with platinum-based chemotherapy, which often causes serious side effects and offers limited long-term benefit. Many patients are even ineligible for it due to underlying health conditions. The new combination presents a more effective and better-tolerated alternative, as shown in recent clinical trials reviewed by the authors. Enfortumab vedotin targets Nectin-4, a protein present in most urothelial cancer cells, delivering a cancer-killing agent directly into tumors. Pembrolizumab helps the immune system detect and destroy cancer cells. Together, they have shown strong results in extending survival with fewer serious side effects than chemotherapy. These findings led to FDA approval in 2023 for use in a broad range of patients, including those unable to tolerate traditional treatments. “In the phase II KEYNOTE-052 study, pembrolizumab demonstrated significant efficacy as initial therapy in patients with aUC who were ineligible for a cisplatin-based regimen.” The review also compares this new approach with other evolving strategies, such as therapies using nivolumab and chemotherapy combinations. Among current first-line options, enfortumab vedotin and pembrolizumab have produced the most promising outcomes. However, the best course of action following disease progression remains unclear. Other important challenges raised in the review include the high cost of the new therapies, limited patient access to them, and the absence of reliable biomarkers to predict individual response. The authors call for further studies to refine treatment strategies and explore blood-based tools that could guide therapy decisions and minimize side effects. This review offers a clear summary of how recent clinical advances are reshaping the treatment of aUC. It reflects a shift away from traditional chemotherapy toward immunotherapy and targeted, personalized treatments that aim to extend survival and improve quality of life. DOI - https://doi.org/10.18632/oncotarget.28741 Correspondence to - Elias Antoine Karam - eliaskaram18@gmail.com Video short - https://www.youtube.com/watch?v=VrTXaF2qW2k Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28741 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, advanced urothelial carcinoma (aUC), enfortumab vedotin, pembrolizumab, treatment strategies, bladder cancer To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

The discussion reveals the intriguing variations of HER2 mutations in non-small cell lung cancer among patients in northeastern Brazil. Researchers highlight the significant genetic diversity and the associated treatment gaps that hinder effective care. The need for improved access to molecular testing and targeted therapies is emphasized, particularly in underrepresented populations. This exploration sheds light on a previously overlooked area of cancer research, contributing vital insights to the global understanding of lung cancer.

Explore the innovative journey of a 62-year-old man battling metastatic colorectal cancer. With five previous treatment lines, the case reveals the crucial role of precision oncology. The discussion delves into how personalized treatment plans are tailored based on unique genetic mutations found in the tumor, showcasing advancements in cancer care. Discover the challenges of medication access and trial enrollment in the quest for effective therapies against one of the deadliest cancers worldwide.

Researchers discuss the surprising link between the CHEK2 gene and immunotherapy effectiveness in solid tumors. CHEK2, known for DNA repair, may also impact how tumors respond to immune system attacks. When CHEK2 function declines, tumors might develop more mutations, producing recognizable neoantigens. These signals help the immune system pinpoint and destroy cancer cells more efficiently. This new understanding opens exciting avenues for improving treatment outcomes and developing biomarkers in cancer therapy.

A recent study uncovers a rare success story in pancreatic cancer treatment, revealing that some patients respond remarkably to immunotherapy. This challenges the notion that immunotherapy is ineffective for this aggressive cancer type. With 82% of participants showing tumor shrinkage, the findings prompt a reevaluation of treatment strategies and highlight the potential for personalized medicine. The need for improved clinical trial designs and biomarker use to better target therapies is emphasized, offering hope for future advancements in treatment.

Bladder cancer poses a serious health challenge, with tens of thousands of new cases each year. The podcast discusses innovative combinations of radiation therapy and immunotherapy as a promising treatment approach. Recent clinical trials highlight the potential for better patient outcomes and reduced side effects. The exploration of biological mechanisms underlying this synergy adds depth to the conversation, suggesting a hopeful path forward for patients with advanced or recurrent bladder cancer.

Delve into the complexities of cardio-oncology, where balancing cost, quality, and time is vital for effective care. The discussion highlights how advanced diagnostics and team collaboration between oncologists and cardiologists can enhance patient outcomes while navigating financial challenges. Discover how digital tools and AI are reshaping patient care, making it more efficient and accessible. This timely conversation illuminates the critical need for a holistic approach in managing the heart issues arising from cancer treatments.

A remarkable case sheds light on a patient with advanced non-small cell lung cancer who experienced an exceptional response to amivantamab after other treatments failed. This individual, harboring rare EGFR mutations G719A and A289V, saw significant tumor shrinkage and complete resolution of brain metastases. The podcast explores the implications of this treatment, showcasing hope for individuals with uncommon genetic profiles facing limited options. This breakthrough paves the way for further research into effective therapies for challenging cancer cases.

BUFFALO, NY — June 10, 2025 — The Ride for Roswell, one of the USA’s largest cycling events supporting cancer research, returns to Buffalo on Saturday, June 28, 2025. Hosted annually by Roswell Park Comprehensive Cancer Center, this community-wide event brings together riders, volunteers, and supporters to raise funds for cancer research, celebrate survivors, and honor those lost to the disease. Among the returning participants is the Open Access Team, led by team captain Sergei Kurenov. This year, the team is once again proudly sponsored by Impact Journals, the publisher of open access journals Oncotarget, Aging, Genes & Cancer, and Oncoscience. “For the last 10 years, I have continuously participated in the Ride for Roswell in honor of those who have bravely fought cancer,” said Kurenov. “This journey is deeply personal for me. My father battled cancer, and some of my closest friends have fought through prostate and lung cancer with incredible strength.” This year, the Open Access Team rides in honor of Dr. Mikhail (Misha) Blagosklonny, a visionary scientist who dedicated his career to advancing cancer and aging research. As the founding Editor-in-Chief of Oncotarget, Aging, and Oncoscience, Dr. Blagosklonny was a pioneer of open-access publishing. His groundbreaking work on mTOR signaling and rapamycin transformed our understanding of cancer biology and healthy lifespan extension. The 2025 Ride for Roswell features nine route options, ranging from 4 to 100 miles, all beginning at the University at Buffalo North Campus. Riders from across the USA and beyond are invited to participate and make a meaningful impact in the fight against cancer. This ride is more than just a journey on two wheels—it’s a commitment to building a future where no one has to fear a cancer diagnosis. There is still time to support the Open Open Access Team in the 2025 Ride for Roswell. Whether by donating, joining the team, or sharing their story, every action brings us closer to better treatments, deeper understanding, and, ultimately, a cure. Visit the Open Access Team page - https://give.roswellpark.org/site/TR/SpecialEvents/General?team_id=23320&pg=team&fr_id=2020 About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science). To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

Cigarette smoke significantly hampers the body's ability to repair DNA, increasing lung cancer risk. A key protein, XPC, is crucial for mending DNA damage, and low levels are linked to cancer development. The researchers reveal a dual mechanism at play, where smoke and reduced DNA repair capabilities work together, highlighting the importance of prevention efforts. Understanding these early changes can lead to new strategies for those at heightened risk for lung cancer.