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The Ó³»­´«Ã½â€™s Cancer Dependency Map Consortium (DMC) is an academic-industry collaboration that has transformed the study of cancer by developing one of the most comprehensive inventories of tumor vulnerabilities. Launched in late 2018, the DMC is entering its third phase, building on years of foundational research to accelerate the discovery and understanding of novel oncology targets and biomarkers for the next generation of cancer therapies.

The DMC supports the generation of high-quality datasets and exploratory tools that have systematically driven the discovery of genetic and chemical vulnerabilities in cancer. The consortium pioneers and scales new technologies, including advanced cancer models, functional genomics approaches, large-scale drug sensitivity screening through PRISM, and emerging multi-omics and single-cell approaches. The DMC also leads in the development of dependency analytics and software. 

"We have reached a pivotal moment where we can significantly accelerate cancer precision medicine," said William Sellers, core institute member at the Ó³»­´«Ã½ and director of the institute’s Cancer Program. "DMC 3.0 is designed to bridge the gap between functional genomics and therapeutics by systematically addressing resistance and leveraging new modalities like cell surface targets, to define how we can selectively kill cancer cells."

The DMC is powered by a robust alliance of industry leaders, including:

• AbbVie
• Amgen
• Bayer
• Bristol Myers Squibb
• Boehringer Ingelheim
• Deciphera, a member of Ono Pharma
• Exelixis
• Genentech, a member of the Roche Group
• Gilead
• GSK
• IDEAYA Biosciences
• Incyte
• Johnson & Johnson
• Eli Lilly and Company
• Merck (known as MSD outside of the United States and Canada)
• Novartis
• Pfizer
• Pierre Fabre Laboratories
• Revolution Medicines
• Roche
• Servier
• Takeda

A foundation of scale

The launch of this next phase follows the successful completion of DMC 2.0, which dramatically expanded the Cancer Dependency Map (DepMap) resource. The cancer cell line collection grew to over 2,000 models across diverse human cancer subtypes, including 3D models such as organoids and spheroids. Using the PRISM platform, 400 compounds were screened across 900 cancer cell lines, and combinatorial screens were leveraged to unmask critical dependencies hidden due to paralog redundancy. The researchers also generated a variety of new multi-omics datasets and new analytical and software tools, aiding research toward the discovery of new predictive biomarkers.

Notable targets identified through this work include the WRN helicase in MSI+ cancers and PRMT5 in MTAP/CDKN2A co-deleted cancers — both of which have led to therapeutic candidates tested in clinical trials. Most recently, the consortium identified the ribosomal rescue protein PELO as a vulnerability in chromosome 9p21-deleted or MSI cancers.

"The Cancer Dependency Map Consortium at the Ó³»­´«Ã½ provides an indispensable atlas for next generation precision medicine," said Dale Porter, head of US research at Servier. "By systematically mapping the genetic and pharmacologic vulnerabilities of cancer — including inaccessible patient-derived models — the DMC has created a powerful engine for high-confidence target discovery and the identification of predictive biomarkers that ensure the right drugs reach the right patients. Furthermore, the integration of the PRISM screening platform is a game-changer. Its ability to evaluate hundreds of compounds across hundreds of diverse cell lines provides unprecedented speed and depth in drug discovery. At Servier, we are especially looking forward to how it will allow us to visualize the therapeutic potential of new leads and reference molecules."

Targeting resistance and new modalities

DMC 3.0 aims to support early discovery for newer therapeutic modalities and address the challenges of therapeutic resistance. Key focus areas for new data and software tools include:

• Expanding multi-omics profiling with new Ó³»­´«Ã½ technologies to identify novel synthetic lethal targets and better define patient populations
• Systematically cataloging novel and existing surface proteins to guide biologics and cell-based therapies
• Addressing resistance by mapping vulnerabilities in the resistance setting 
• Integrating patient-derived data directly into the models to accelerate the path to therapeutics
• Using high-dimensional readouts to identify key targets that were previously missed 

Academic scientists, industry researchers, and biotech investors alike rely on this target discovery platform to de-risk drug development. The contributions of this program continue to propel new clinical programs and support the launch of new biotech companies.

"The impact of the resource generated by the DMC is clear: It’s a catalyst for the entire oncology community," said Francisca Vazquez, director of the at the Ó³»­´«Ã½. "In Phase 3, we are providing a roadmap for the next decade of precision medicine, moving the field beyond cataloging cancer’s weaknesses to enabling the development of next-generation, safer medicines."