NCI Center for Cancer Research

Type IA topoisomerases (TopoIAs) are present in all living organisms. They resolve DNA/RNA “tangles” by breaking and rejoining single-stranded DNA/RNA segments and allowing the passage of another nucleic acid segment through the break. CCR researchers revealed in a new study published in Nature how TOP3B, one of these topoisomerases, catalyzes both DNA and RNA relaxation, while TOP3A acts only on DNA.   CCR’s Developmental Therapeutics Branch (DTB) focuses on cancer-specific genomic and epigenomic alterations, oxidative signaling, molecular pharmacology and drug resistance. Through the understanding of molecular mechanisms in healthy cells, the DTB provides insights for scientists to understand how these processes may go awry and cause diseases like cancer.  Read more: https://go.nih.gov/DxCWD4j Image: Cryo-EM volume of cTOP3B-Y336F bound to gapped DNA (after applying a gaussian filter) in orthogonal views. Colored regions highlight the protein segments of the core complex of TOP3B-TDRD3 (cTOP3B) resolved from the cryo-EM volumes. National Cancer Institute (NCI), National Institutes of Health (NIH): Intramural Research Program (IRP)

The use of tumor-infiltrating T lymphocytes (TIL) to target cancer neoantigens has led to lasting remissions in patients with metastatic melanoma and certain cases of metastatic epithelial cancer. However, this process is laborious and time-consuming, and it relies on the availability of surgically removed tissue. A team of CCR researchers found that screening libraries with archived tumor data could be used to discover most neoantigens present in metastatic tumors that require treatment, potentially accelerating TIL screening for therapies without requiring surgery. If applied early in disease progression, the approach could help identify neoantigens for future T-cell receptor-based therapies.  Read more: https://go.nih.gov/iwmkiGk National Cancer Institute (NCI), National Institutes of Health (NIH): Intramural Research Program (IRP)

March is Kidney Cancer Awareness Month and a great time to reflect on some of the kidney cancer research done at the Center for Cancer Research. CCR researchers discovered that a treatment being tested in patients with bladder cancer was surprisingly effective in patients with kidney cancer. Following clinical testing and collaborative research, it’s now considered a first-line therapy for patients with renal cell carcinoma, the most common form of kidney cancer. Read more: https://go.nih.gov/XRLcUB2  National Cancer Institute (NCI)

A recent study led by researchers in CCR’s Developmental Therapeutics Branch shows how targeting two proteins that cancer cells rely on for metabolism and DNA repair can double the survival rate of mice with lung cancer tumors. The initial analysis suggests that these findings may translate to humans. Read more: https://go.nih.gov/U86Xy9p  Learn more about CCR’s Developmental Therapeutics Branch: https://go.nih.gov/H0Em4Vh Left image: non-small cell lung cancer cells A549 treated with an ATM inhibitor drug. Right image: non-small cell lung cancer cells A549 lacking PRDX1 and treated with an ATM inhibitor drug. CREDIT: Haojian Li et al. National Cancer Institute (NCI), National Institutes of Health (NIH): Intramural Research Program (IRP)

March is Myeloma Awareness Month, but our researchers are investigating the disease year-round. CCR is leading a clinical trial studying a radiotracer that may be a useful detection method for multiple myeloma. The goal is to find ways to identify the disease earlier when it returns.  Read more about this trial: https://go.nih.gov/MgVXRhG  Search all CCR clinical trials: https://go.nih.gov/QmcCTlW  National Cancer Institute (NCI), NIH Clinical Center (CC)

In a new discovery, researchers in CCR’s Developmental Therapeutics Branch show how DNA synthesis recovers after cells encounter double-strand breaks, when both strands of the DNA double helix are broken. This answers the central question of how cancer cells continue to replicate even after sustaining damage from anti-cancer treatments that can cause these breaks. If researchers can find a way to block this repair process, it could be a new way to treat cancer.  Read more: https://go.nih.gov/LErkzJh  Learn more about CCR’s Developmental Therapeutics Branch: https://go.nih.gov/H0Em4Vh  Image: Detection of DNA breakage (green) and DNA synthesis (magenta) in the cell nucleus reveals a novel cellular mechanism that prevents the initiation of DNA replication at chromatin loops adjacent to double-stranded DNA breaks, without affecting global DNA synthesis. National Cancer Institute (NCI), National Institutes of Health (NIH): Intramural Research Program (IRP)

Abnormalities in a gene called BRCA2 are linked to increased risk of breast and ovarian cancers, as well as several other types of cancer. Despite its significance, little is known about many of the thousands of variants in BRCA2 that occur in humans that lead to increased risk. Now, a new study led by CCR investigators has used CRISPR technology to classify over 6,500 known and potential variants as benign or likely to cause cancer.    “If someone inherits a mutation and our work shows that it is benign, you can imagine the relief it will give them,” said Shyam K. Sharan, Ph.D., the lead author on the study.    Read more: https://go.nih.gov/VAFeXPn     Image: BRCA2 protein with a sliding scale of color indicating the regions containing certain variants. Blue regions contain benign variants, while red regions contain pathogenic regions. National Cancer Institute (NCI), National Institutes of Health (NIH): Intramural Research Program (IRP)

In recognition of World Kidney Day, meet Katie Coleman, a CCR patient who has shared her story of treatment at the NIH Clinical Center (CC). When Katie was diagnosed with a very rare form of advanced kidney cancer in 2020, she enrolled in an NCI clinical trial to have surgery in hopes of removing her tumors. Today, she’s an author and advocate, sharing her journey through social media and her recently published book.  “NIH’s approach to everything is extremely thorough,” Katie said. “It helped reassure me that each doctor I met with told me they have never prepared for a case quite as much as they prepared for mine.” Read Katie’s story: https://go.nih.gov/XFGR0q9 Learn more about kidney (renal cell) cancer: https://go.nih.gov/7gtXCoI  National Cancer Institute (NCI)

A clinical trial led by researchers in CCR’s Center for Immuno-Oncology and Surgical Oncology Program demonstrated the effectiveness of the novel treatment PRGN-2012 against recurrent respiratory papillomatosis (RRP) in adults. The results serve as the foundation for an application for accelerated approval to the U.S. Food and Drug Administration (FDA).   “We feel this really changes the way that adults with RRP in the United States will be treated, and we think this treatment has the possibility of eliminating many procedures that patients would have to receive otherwise,” said Scott Norberg, D.O., the Principal Investigator of the clinical trial. Read more: https://go.nih.gov/PEGSdKV Image: An illustration of papillomas in the throat, caused by recurrent respiratory papillomatosis. National Cancer Institute (NCI), National Institutes of Health (NIH): Intramural Research Program (IRP), NIH Clinical Center (CC)

This clinical trial was conducted in CCR’s Pediatric Oncology Branch to expand treatment options for people with neurofibromatosis type 1 (NF1). People with NF1 can develop a kind of nerve tumor, called plexiform neurofibroma, that cannot easily be treated by surgery. This clinical trial of selumetinib in 33 adults showed that the drug can shrink the size of tumors in the majority of patients and relieve their symptoms, such as pain. Read the full article: https://go.nih.gov/kzCivf4  Learn more about CCR’s Pediatric Oncology Branch: https://go.nih.gov/7RVzO8W