Cancer

Protein production or translation is tightly coupled to a highly conserved stress response—the heat shock response and its primary regulator, heat shock factor 1 (HSF1)—that cancer cells rely on for survival and proliferation, according to Whitehead Institute researchers. In mouse models of cancer, therapeutic inhibition of translation interrupts HSF1’s activity, dramatically slowing tumor growth and potentially rendering drug-resistant tumors responsive to other therapies.

Whitehead Institute researchers have determined that in basal breast cancer cells a transcription factor known as ZEB1 is held in a poised state, ready to increase the cells’ aggressiveness and enable them to transform into cancer stem cells capable of seeding new tumors throughout the body. Intriguingly, luminal breast cancer cells, which are associated with a much better clinical prognosis, carry this gene in a state in which it seems to be permanently shut down.

Whitehead Institute researchers have identified a protein complex that, when mutated, sends the master growth regulatory pathway known as mTORC1 into overdrive. Researchers believe that mutations in this complex could serve as biomarkers to predict response to rapamycin treatment in cancer patients.

In a surprising finding that helps explain fundamental behaviors of normal and diseased cells, Whitehead Institute scientists have discovered a set of powerful gene regulators dubbed “super-enhancers” that control cell state and identity.

According to Whitehead Institute researchers, a protein known as monocarboxylate transporter 1 (MCT1), which is highly expressed in a subset of metabolically altered cancer cells, is needed for the entry of the investigational cancer drug 3-bromopyruvate (3-BrPA) into malignant cells.

Whitehead Institute researchers have determined the mechanism used by c-Myc to increase the expression of all active genes in cancer cells. Elevated levels of c-Myc are linked to increased rates of metastasis, disease recurrence, and mortality in cancer patients. Guided by this new model, researchers hope to find ways to restrict c-Myc's activity to eradicate cancer cells that become dependent on c-Myc for their survival.

Whitehead Institute researchers have found that an ancient, highly conserved cell survival factor drives expression of a specific set of genes that is strongly associated with metastasis and death in patients with breast, colon, and lung cancers.

A clinical trial involving collaboration between researchers at Whitehead Institute and Dana Farber Cancer Institute is now enrolling patients with recurrent or metastatic estrogen receptor-positive (ER+) breast cancer.