A genetic fault long believed to drive the development of esophageal cancer may in fact play a protective role early in the disease, according to new research published in Nature Cancer. This unexpected discovery could help doctors identify which individuals are at greater risk of developing cancer, potentially leading to more personalised and effective preventive strategies. 

Tumor cells circulating in the blood are the “germ cells” of breast cancer metastases. They are very rare and could not be propagated in the culture dish until now, which made research into therapy resistance difficult. A team from the German Cancer Research Center (DKFZ), the Heidelberg Stem Cell Institute HI-STEM* and the NCT Heidelberg** has now succeeded for the first time in cultivating stable tumor organoids directly from blood samples of breast cancer patients. Using these mini-tumors, the researchers were able to decipher a molecular signaling pathway that ensures the cancer cells' survival and resistance to therapy. With this knowledge, the team was able to develop an approach to specifically eliminate these tumor cells in lab experiments.

Largescale changes in the genome inherited from parents are significant risk factors for pediatric solid tumors, such as Ewing sarcoma, neuroblastoma, and osteosarcoma, according to a new study. The findings, which highlight the role of germline structural variants (SVs) in early genome instability, provide new insights into the genetic underpinnings of pediatric cancers and open doors for improved diagnostic and treatment strategies. Unlike adult cancers, which often result from environmental factors or DNA damage built up over time, childhood cancers develop too quickly for these mechanisms to play a major role. Such an early age of onset suggests that germline genetic factors are involved. Although studies suggest a 4.5-fold increased familial risk for pediatric solid tumors, only 10–15% of cases can be attributed to known pathogenic germline variants.  Here, Riaz Gillani and colleagues conducted a comprehensive analysis of rare germline SVs in pediatric extracranial solid tumors using whole-genome sequencing from 1,765 affected children and 943 unaffected relatives. They sought to determine inheritance patterns. They evaluated 6,665 unrelated adult controls for comparison. The germline genome sequencing analysis identified 84 rare, large (larger than 1megabase) unbalanced chromosomal abnormalities – alterations involving the gain or loss of genetic material – associated with an increased risk of pediatric solid tumors, particularly in males. According to the findings, these abnormalities were predominantly inherited from unaffected parents (82%), with a smaller proportion (18%) arising de novo. In addition to large chromosomal abnormalities, smaller gene-disruptive germline SVs were identified as risk factors for pediatric tumors, absent in controls but present in cancers like neuroblastoma and Ewing sarcoma. These SVs included disruptions of DNA repair genes such as BARD1 and genes involved in tumorigenesis. Overall, Gillani et al. estimate that rare germline SVs explain up to 5.6% of an individual’s total liability for childhood cancer. In a Perspective, Jayne Hehir-Kwa and Geoff Macintyre discuss the study and its findings in greater detail.

A new study by investigators from Mass General Brigham uncovers how a novel immunotherapy prevents squamous cell carcinoma, with benefits lasting five years after treatment. This therapy is the first to activate specific components of the adaptive immune system, particularly CD4+ T helper cells, which are not known to be involved in traditional cancer treatments. This work highlights the potential for similar immunotherapies to prevent other cancers throughout the body. Results are published in the Journal of Clinical Investigation. 

Researchers at the University of Colorado Anschutz Medical Campus have discovered that some CAR-T cells engineered to fight cancer and other conditions carry the memory of past encounters with bacteria, viruses and other antigens within them, a finding that may allow scientists to manufacture the cells in more precise and targeted ways.

 Most study participants could not extract basic information—including whether they have cancer—from standard prostate cancer pathology reports but were able to understand this diagnostic information from the patient-centered pathology reports (PCPRs). Also, they discriminated between risk levels (i.e., lower levels of perceived worry in the low-risk condition) with PCPRs compared with standard reports. Hospital systems should consider including PCPRs with standard pathology reports to improve patient understanding. 

This case-control study found that individuals with more advanced breast cancer at diagnosis were more likely to have prevalent cardiovascular disease. This finding may be specific to hormone receptor–positive and ERBB2-negative (formerly HER2) disease. Future studies are needed to confirm these findings and investigate interventions to improve patient outcomes, including personalized cancer screening.