Triple-negative Breast Cancer - Research Directions

Research Directions

Angiogenesis and EGFR (HER-1) inhibitors are frequently tested in experimental settings and have shown efficacy. Treatment modalities are not sufficiently established for normal use, and it is unclear in which stage they are best used and which patients would profit.

PARP inhibitors showed some promise in early trials but failed in some later trials. A novel antibody-drug conjugate known as Glembatumumab vedotin (CDX-011), which targets the protein GPNMB, has also shown encouraging results in recent clinical trials.

Triple-negative breast cancers have, on average, significantly higher fluorine-18 fluorodeoxyglucose (FDG) uptake (measured by the SUVmax values) compared with uptake in ER+/PR+/HER2- tumors using fluorine-18 fluorodeoxyglucose-positron emission tomography (FDG-PET). It is speculated that enhanced glycolysis in these tumors is probably related to their aggressive biology.

A number of new strategies are currently being tested in clinical trials, including the PARP inhibitor BSI 201, NK012, and the GPNMB targeted CDX-011.

The widely-used diabetes drug metformin holds promise for the treatment of triple-negative breast cancer. In addition metformin may influence cancer cells through indirect (insulin-mediated) effects, or it may directly affect cell proliferation and apoptosis of cancer cells. Epidemiologic and preclinical lab studies indicate that metformin has anti-tumor effects, via at least two mechanisms, both involving activation of the AMP-activated protein kinase (AMPK). A large-scale phase III trial of metformin in the adjuvant breast cancer setting is being planned.

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