New Discoveries and Honors

A major challenge in treating brain cancer is delivering drugs across the blood-brain barrier (BBB), the dense network of cells and blood vessels that prevents toxins and pathogens from entering the brain. Unfortunately, the BBB also bars entry to therapeutic molecules, leaving highly toxic radiation or chemotherapy treatment as the only recourse for many patients with brain cancer.

Cancer immunotherapies work by triggering the body’s immune response against tumors. Tumor cells can evade destruction by the immune system, however, by attracting helper T cells, the “peacekeepers” of the immune system.

Glioblastomas (GBMs) are the most common—and the most aggressive—type of cancer originating in the brain. Part of the reason these tumors are so hard to treat is that the cancer cells suppress the immune cells that enter their environment. Not only can they outcompete immune cells for critical nutrients, effectively starving the immune cells, but some GBMs can even adjust their metabolism to produce metabolites that directly inhibit immune cell activity.

P53, the most frequently mutated gene across all human cancers, is mutated in the majority of pancreatic cancers. But despite the overwhelming evidence that p53 mutations contribute to cancer progression, therapies targeting mutant p53 have had limited success, suggesting an incomplete understanding of the protein’s function. In order to understand what goes wrong when p53 mutates, researchers need a clearer picture of how normal p53 prevents tumor development in the first place.

Human papillomavirus (HPV) was first identified as a cancer driver in the 1970s, when a German doctor named Harald zur Hausen discovered that the virus causes about 75% of human cervical cancers. HPV has since been linked to several other types of human cancer, including head and neck cancer, as discovered by then-Damon Runyon Clinical Investigator Maura L. Gillison, MD, PhD, in 2000.

Cancer cells are often assumed to be “hypermetabolic,” meaning their energy-producing cycles run on overdrive to fuel the uncontrolled division and growth that defines a tumor. But new findings from former Damon Runyon Fellow Caroline R. Bartman, PhD, and her colleagues at Princeton University challenge this assumption, revealing how much we still have to learn about cancer metabolism.

The process of transcription, in which DNA is copied into RNA, is carried out by a complex cellular machinery that controls which genes are expressed as proteins. Researchers have observed certain organizational features of this machinery, such as the clumping of certain proteins into “condensates,” which function as a unit though unbound by a membrane.

Messenger RNA conveys instructions for how to build a protein in the form of codons—sequences of three nucleotides (A, C, G, or U) that correspond to a specific amino acid. The codons CGU, CGC, and CGA, for example, all correspond to the amino acid arginine. During the process of translation, ribosomes move along the messenger RNA, “reading” out the codons and building a chain of amino acids as translational RNAs (tRNAs) deliver them one by one.

Chimeric antigen receptor (CAR) T cell therapy, in which a patient’s own immune T cells are genetically engineered to target their cancer cells, is one of the most promising advances in cancer therapy of the past decade. Having demonstrated the effectiveness of CAR T cells against a range of blood cancers, researchers now seek to design CAR T cells that can remain active in the body for longer and more efficiently eliminate tumors, with the goal of reducing costs and bringing CAR T therapy to more patients.

Cell adhesion molecules (CAMs) are proteins found on the cell surface that facilitate interactions between cells. They are responsible for organizing and binding cells within tissue structures, creating circuits between neurons, and chaperoning immune cells to their destinations. Known as “cellular glue” and essential for organ function, CAMs are found throughout the body.

Small-cell lung cancer (SCLC), which accounts for about 15% of lung cancer diagnoses, is a relatively rare but aggressive disease. Most SCLC patients respond to chemotherapy at first, but nearly all experience disease recurrence, and at that point treatment options become scarce. Because SCLC is driven by mutations that knock out “tumor suppressor” genes, rather than activate cancer driver genes, it has been difficult to treat with targeted therapies.