Research

Pleiotropic Mechanisms Drive Endocrine Resistance in the 3D Bone Microenvironment

Hormonal therapy (HT) inhibits the growth of hormone receptor-positive (HR+) breast (BrCa) and prostate (PrCa) cancers, but resistance to HT frequently develops within the complex metastatic microenvironment of the host organ (often the bone), a setting poorly recapitulated in 2D culture systems. To address this limitation and to study the potential contribution of cell non-autonomous mechanisms to endocrine resistance, first author Eugen Dhimolea, PhD, and senior author Constantine Mitsiades, MD, PhD, share a new study in American Association for Cancer Research, wherein they examined the responses of BrC and PrCa cells to HT in 3D culture conditions in the presence vs. absence of bone marrow stromal cells (BMSC) in the microenvironment of key metastatic sites.

Dana-Farber Collaborates with Mass Eye and Ear to Rebuild Damaged Corneas Using Patient-Derived Stem Cells

Under the direction of principal investigator Ula V. Jurkunas, MD, a cornea and refractive surgeon at the Massachusetts Eye and Ear Infirmary, and Jerome Ritz, MD, Senior Director of the Connell and O'Reilly Families Cell Manipulation Core Facility (CMCF) at Dana-Farber, surgeons and researchers collaborated in four cases of corneal stem cell transplant, which represent the first procedures of their kind to occur in the United States and are all part of an ongoing clinical trial supported by the National Eye Institute of the National Institutes of Health (NIH).

Dana-Farber Opens Clinical Trial to Evaluate Next-Generation Sequencing Blood Test to Detect Cancer

Dana-Farber is opening a new clinical trial for enrollment to evaluate a minimally-invasive blood test that will look for the earliest signs of cancer which may be present in the blood stream before the disease has progressed to a point where it causes symptoms. The clinical trial uses a blood test developed by GRAIL, Inc. that could detect more than 50 types of cancer, as well as their location within the body. In previous studies, cancers were detected across all stages (stage I–III sensitivity: 43.9%; stage I–IV sensitivity: 54.9%) at a specificity of >99% and a single false positive rate of <1%. The blood test uses next-generation sequencing to analyze the methylation pattern on the DNA of cancer cells that are circulating in the bloodstream.

Increased Lysosomal Biomass is Responsible for the Resistance of Triple-Negative Breast Cancers (TNBC) to Treatment with CDK4/6 Inhibitors

Consistent with their growth-promoting roles, overexpression of cyclin D–CDK4/6 kinases has been documented in a large number of human malignancies, including breast cancer. However, in contrast to hormone receptor–positive breast cancers, which initially respond to treatment with CDK4/6 inhibitors like palbociclib, triple-negative breast cancers (TNBC) show an intrinsic resistance to CDK4/6 inhibition.

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