Cold and hot tumors: from molecular mechanisms to targeted therapy

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 18, 2024

Immunotherapy has made significant strides in cancer treatment, particularly through immune checkpoint blockade (ICB), which shown notable clinical benefits across various tumor types. Despite the transformative impact of ICB treatment therapy, only a minority patients exhibit positive response to it. In with solid tumors, those who respond well typically demonstrate an active profile referred as "hot" (immune-inflamed) phenotype. On other hand, non-responsive may distinct "cold" (immune-desert) phenotype, differing from features tumors. Additionally, there is more nuanced "excluded" positioned between and categories, known type. Effective differentiation understanding intrinsic factors, characteristics, TME, external factors are critical for predicting results. It widely accepted that therapy exerts profound effect on limited efficacy against or "altered" necessitating combinations therapeutic modalities enhance cell infiltration into tissue convert tumors ones. Therefore, aligning traits this review systematically delineates respective influencing extensively discusses varied approaches drug targets based assess efficacy.

Language: Английский

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Enfortumab Vedotin und Pembrolizumab

Deleted Journal, Journal Year: 2025, Volume and Issue: 64(1), P. 60 - 74

Published: Jan. 1, 2025

The aim of this article is to raise awareness among healthcare providers about the adverse events (AEs) associated with combined treatment enfortumab vedotin and pembrolizumab. differential diagnostic allocation these AEs respective agents discussed, overlaps between side effect profiles two drugs are identified strategies for an effective management presented. recommendations based on currently valid prescription information both drugs, results pivotal approval studies guidelines recognized specialist organizations as well clinical experience authors.

Language: Английский

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An Adverse Double-Hit by Pembrolizumab: A Case Report of Bullous Pemphigoid and Pneumonitis

Journal of Medical Cases, Journal Year: 2025, Volume and Issue: 16(2), P. 69 - 76

Published: Feb. 1, 2025

Immune checkpoint inhibitors like pembrolizumab represent a modern approach to the management of various malignancies, including non-small cell lung cancer. The therapeutic activity immunotherapy is exerted by activation immune cells against tumor cells. However, systemic system can lead development autoimmune complications known as immune-related adverse events. A combination rare events occasionally observed simultaneously in same patient. We present case 66-year-old male with squamous carcinoma who presented emergency department dyspnea and respiratory failure. Imaging findings were consistent pulmonary embolism nonspecific interstitial pneumonitis. One month before this event, he was diagnosed bullous pemphigoid following 21 cycles treatment pembrolizumab. radiological findings, lack response antibiotics, negative microbiological workup, excellent corticosteroids established diagnosis pembrolizumab-induced pneumonitis secondary rare; only few reports exist literature. Hence, highlights possibility multiple exclusion infectious diseases other immunologic disorders similar clinical presentation necessary make final start appropriate treatment. Serology, histopathology, direct immunofluorescence aid pemphigoid; differential includes or lichenoid diseases, Stevens-Johnson syndrome/toxic epidermal necrolysis, drug reaction eosinophilia symptoms. Imaging, testing, bronchoscopy (if possible) confirm pneumonitis, which should be differentiated from acute coronary syndrome, cardiogenic edema, embolism, progression, lower tract infections (especially Pneumocystis jirovecii pneumonia immunocompromised patients). An interdisciplinary for these cases.

Language: Английский

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Toxicities and management strategies of emerging antibody–drug conjugates in breast cancer

Therapeutic Advances in Medical Oncology, Journal Year: 2025, Volume and Issue: 17

Published: Jan. 1, 2025

Antibody–drug conjugates (ADCs) offer a promising therapeutic approach for various cancers, enhancing the window while mitigating systemic adverse effects on healthy tissues. ADCs have achieved remarkable clinical success, particularly in treating breast cancer, becoming standard therapy across all subtypes, including hormone receptor-positive, human epidermal growth factor receptor 2-positive, and triple-negative cancer. Although designed to selectively target antigens via monoclonal antibodies, can exhibit toxicity normal tissues, often due off-target of their cytotoxic payloads. Understanding managing these toxicities according established guidelines are crucial ADC efficacy, minimizing events, ultimately improving patient outcomes. This review comprehensively examines employed cancer treatment explores management strategies. Furthermore, we investigate novel beyond trastuzumab deruxtecan sacituzumab govitecan, evaluating potential efficacy corresponding safety profiles.

Language: Английский

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Enfortumab vedotin and pembrolizumab: redefining the standard of care for previously untreated advanced urothelial cancer

Future Oncology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 16

Published: March 25, 2025

Combination treatment with Enfortumab vedotin (EV), an antibody drug conjugate targeting Nectin-4 a monomethyl auristatin E (MMAE) payload, and pembrolizumab, programmed death 1 (PD-1) inhibitor, has become the new standard of care for previously untreated locally advanced or metastatic urothelial carcinoma. In recently published phase III study, EV-302, EV pembrolizumab demonstrated improved outcomes compared to platinum-based chemotherapy, including objective response rate, progression free survival, unprecedented median overall survival 33.8 months (versus 15.9 months; hazard ratio 0.51; 95% confidence interval 0.43–0.61; p < 0.00001). We reviewed mechanism action, clinical efficacy, exploratory biomarkers, safety profile as monotherapies combination in cancer.

Language: Английский

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Lines of Therapy for Locally Advanced/Metastatic Urothelial Carcinoma: The New Paradigm

JCO Oncology Practice, Journal Year: 2025, Volume and Issue: unknown

Published: April 4, 2025

Urothelial carcinoma (UC) is the most common malignancy of urinary tract, with urothelial bladder cancer accounting for approximately 90% cases. Metastatic UC (mUC) a particularly aggressive subset that presents significant treatment challenges, especially in patients who are often older than 70 years and have multiple comorbidities. For several decades, cisplatin-based chemotherapy has been standard first-line locally advanced (LA) mUC. However, its utility limited as many ineligible owing to their health status, overall survival rates remain suboptimal. Recent advancements, including antibody-drug conjugates immunotherapies, begun reshape landscape LA/mUC. The combination enfortumab vedotin pembrolizumab shown promising clinical outcomes. approval novel drugs therapies not only provides new opportunities patient care but also creates need physicians adapt this evolving therapeutic paradigm. This review explores latest data on management LA/mUC offers insights into sequencing

Language: Английский

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Reevaluating the role of platinum-based chemotherapy in the evolving treatment landscape for patients with advanced urothelial carcinoma

The Oncologist, Journal Year: 2024, Volume and Issue: 29(12), P. 1003 - 1013

Published: Aug. 21, 2024

Platinum-based chemotherapy has been the standard first-line (1L) treatment for advanced urothelial carcinoma (UC) decades, based on proven efficacy and established safety profiles of cisplatin- carboplatin-based regimens. With emergence novel regimens, it is important to reevaluate contextualize role 1L platinum-based chemotherapy. followed by avelumab maintenance in patients without disease progression following was as a regimen JAVELIN Bladder 100 phase III trial. More recently, EV-302 trial showed superiority enfortumab vedotin (EV) + pembrolizumab versus chemotherapy, Checkmate 901 nivolumab cisplatin/gemcitabine alone. These 2 regimens have now included options guidelines UC. EV preferred treatment, locations where not available or individual are considered suitable, recommended cisplatin-based In this review, we discuss current UC guidelines, practical considerations with maintenance, recent trials cisplatin/gemcitabine, treatments, second-line options.

Language: Английский

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Risk Analysis of enfortumab vedotin: A Real-World Approach Based on the FAERS Database

Heliyon, Journal Year: 2024, Volume and Issue: 10(18), P. e37544 - e37544

Published: Sept. 1, 2024

Language: Английский

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Evolving Treatment Landscape of Frontline Therapy for Metastatic Urothelial Carcinoma: Current Insights and Future Perspectives

Cancers, Journal Year: 2024, Volume and Issue: 16(23), P. 4078 - 4078

Published: Dec. 5, 2024

Cisplatin-based chemotherapy has long been the standard first-line (1L) treatment for metastatic urothelial carcinoma (mUC). However, up to 50% of patients with mUC may be ineligible cisplatin owing comorbidities, necessitating alternative primary options. Immune checkpoint inhibitors (ICIs) have emerged as a vital those unable receive cisplatin. Nevertheless, prognosis advanced UC remains dire and challenges persist in optimizing 1L therapy. Recent medical advancements redirected attention towards innovative drug combinations mUC. The combination enfortumab vedotin (EV) pembrolizumab shown significantly improved overall progression-free survival rates compared alone. This can used who are cisplatin-ineligible or require alternatives chemotherapy. While platinum-based continues essential many patients, approval EV treatments signifies major breakthrough cancer care. These therapies offer enhanced outcomes terms response highlight increasing relevance ICI-containing regimens frontline review provides an exhaustive overview current landscape explores new therapeutic strategies, aim facilitating clinical decision-making guiding strategies

Language: Английский

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