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Ludwig Tumor Atlas: A Focus on Drug Resistance

The Ludwig Tumor Atlas is a collaborative project involving US and European research laboratories that are part of Ludwig Cancer Research Centers and Branches and involves several types of solid cancer. Research at HMS is performed under the auspices of the Ludwig Center at Harvard Medical School. The overall aim of the Atlas is to investigate the molecular basis of intrinsic and acquired resistance to anti-cancer drugs and to develop disease management strategies and therapies that overcome or avoid such resistance. A full description of the projects, data, and publications related to the Ludwig Tumor Atlas can be viewed at the Ludwig Tumor Atlas website.

Drug resistance is the greatest single challenge facing contemporary cancer therapy. Despite extraordinary advances in cancer therapeutics, most patients eventually relapse and succumb to disease due to the development of drug resistance. The problem of resistance is complicated by tumor heterogeneity– both within a single tumor and across a population of patients. Tumors and their microenvironments are also plastic, changing through the course of disease and in response to drugs. High dimensional tissue imaging and single-cell genetics aim to characterize this heterogeneity at multiple spatial and functional scales to improve our understanding of the origins of drug resistance - this understanding is a necessary first step to overcoming resistance in patients. Data are commonly acquired in biopsies from patients prior to and during therapy, and then following relapse. Mouse models of disease are also an important part of this research. An explicit goal of the Ludwig Tumor Atlas is to create and validate image-based clinical tests for next-generation diagnosis and drug development.

Key questions

  • What are the relative roles of changes in the tumor microenvironment and cancer cells themselves in generating drug resistance?
  • Are drug resistant states (and mutations) present prior to the initiation of therapy or are they induced by therapy?
  • Are mechanisms that cause tumors to exhibit intrinsic resistance (drug insensitivity) similar to the mechanisms that make initially sensitive tumors drug resistant (acquired drug resistance)
  • Which among these mechanisms might be targettable using new or existing drugs?

Funding

The Ludwig Tumor Atlas is funded by the Ludwig Center at Harvard Medical School and by a generous gift from the Ludwig Cancer Research Foundation.