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Therapy of advanced melanoma is changing dramatically. Following mutational and biological subclassification of this heterogeneous cancer, several targeted and immune therapies were approved and increased survival significantly. To facilitate further advancements through pre-clinical in vivo modeling, we have established 459 patient-derived xenografts (PDX) and live tissue samples from 384 patients representing the full spectrum of clinical, therapeutic, mutational, and biological heterogeneity of melanoma. PDX have been characterized using targeted sequencing and protein arrays and are clinically annotated. This exhaustive live tissue resource includes PDX from 57 samples resistant to targeted therapy, 61 samples from responders and non-responders to immune checkpoint blockade, and 31 samples from brain metastasis. Uveal, mucosal, and acral subtypes are represented as well. We show examples of pre-clinical trials that highlight how the PDX collection can be used to develop and optimize precision therapies, biomarkers of response, and the targeting of rare genetic subgroups.
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http://dx.doi.org/10.1016/j.celrep.2017.10.021 | DOI Listing |
Bull Math Biol
September 2025
Wolfson Centre for Mathematical Biology, Mathematical Institute, Oxford, UK.
Adaptive therapy (AT) protocols have been introduced to combat drug resistance in cancer, and are characterized by breaks from maximum tolerated dose treatment (the current standard of care in most clinical settings). These breaks are scheduled to maintain tolerably high levels of tumor burden, employing competitive suppression of treatment-resistant sub-populations by treatment-sensitive sub-populations. AT has been integrated into several ongoing or planned clinical trials, including treatment of metastatic castrate-resistant prostate cancer, ovarian cancer, and BRAF-mutant melanoma, with initial clinical results suggesting that it can offer significant extensions in the time to progression over the standard of care.
View Article and Find Full Text PDFJ Oncol Pharm Pract
September 2025
Department of Research & Development, Squad Medicine and Research (SMR), Amadalavalasa, Andhra Pradesh, India.
Cancer vaccines represent a transformative shift in oncology, aiming to prevent malignancies or treat established cancers by training the immune system to recognize tumor-specific or tumor-associated antigens. This review explores the diverse platforms and mechanisms supporting cancer vaccines, ranging from prophylactic vaccines such as HPV and hepatitis B vaccines that have significantly reduced virus-related cancers to therapeutic vaccines like Sipuleucel-T and T-VEC that extend survival in prostate cancer and melanoma. Vaccine types are classified, and delivery platforms including mRNA, peptide, dendritic cell and viral vector-based approaches are examined alongside pivotal clinical trial outcomes.
View Article and Find Full Text PDFRadiol Med
September 2025
Breast Imaging Division, Radiology Department, IEO European Institute of Oncology IRCCS, 20141, Milan, Italy.
Metastatic involvement (MB) of the breast from extramammary malignancies is rare, with an incidence of 0.09-1.3% of all breast malignancies.
View Article and Find Full Text PDFOncol Res
September 2025
Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, 420008, Russia.
Melanoma is a malignant neoplasm with a high propensity to metastasize, arising from melanocytes and contributing significantly to global morbidity and mortality. Despite the demonstrated efficacy of many immunotherapy approaches, these methods rely on direct destruction of tumor cells with minimal impact on the aggregate of nearby non-tumor cells, the extracellular matrix, and blood vessels that form the tumor microenvironment (TME). The TME is known to be heterogeneous and dynamic, exerting both antitumor and pro-tumor effects depending on the specific features and stage of carcinogenesis.
View Article and Find Full Text PDFAdv Healthc Mater
September 2025
Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY, 11794, USA.
Compared to sun-exposed melanomas, acral melanomas are genetically diverse and occur in areas with low sun exposure and high mechanical loads. During metastatic growth, melanomas invade from the epidermis to the dermis layers through dense tumor stroma and are exposed to fibrillar collagen architectures and mechanical stresses. However, the role of these signals during acral melanoma pathogenesis is not well understood.
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