- N Engl J Med 2022; 387:184-186
The authors examine the science behind the induction of objective responses in patients with NSCLC who received adagrasib, an inhibitor of a mutant version of KRAS, which was previously thought to be “undruggable.”
- N Engl J Med 2022; 387:120-131
Adagrasib produced responses in 43% of previously treated patients with non–small-cell lung cancer containing a KRASG12C mutation, with median overall survival of 12.6 months. Regressions of stable brain metastases were noted in one third of evaluable patients. Gastrointestinal toxic effects dominated the adverse events, but fewer than 7%...
- N Engl J Med 2022; 387:180-183
Activating mutations in the KRAS proto-oncogene were identified and characterized more than 40 years ago across several distinct human cancers, including pancreatic and colorectal cancers as well as non–small-cell lung cancer (NSCLC). KRAS somatic alterations are found in approximately 25 to 30% of lung adenocarcinomas and...
- N Engl J Med 2022; 386:2523-2525
The overrepresentation of a silent variant in KRAS led investigators to explore whether this mutation was biologically relevant (it was) and could be exploited in a mouse model to treat KRAS-mutant cancer.
- N Engl J Med 2022; 386:2334-2336
Modified autologous T cells have been successfully used to treat tumors in a small proportion of patients. How can this general approach be used to treat more patients? A recent study of lymphoma, modeled in vitro, points to a potential approach.
- N Engl J Med 2022; 386:2145-2148
This explanatory editorial elucidates the components and concepts behind a study, described in this issue of the Journal, that involves therapeutic targeting of pancreatic cancer with an autologous T cell engineered to have exquisite specificity for targeting the cancer cell.
- N Engl J Med 2022; 386:2138-2138
The editors announce a new article type, the Science behind the Study. The articles, which include illustrations and glossary terms, are meant to elucidate the scientific foundations of new clinical studies published in the Journal.
- N Engl J Med 2022; 386:2143-2144
Pancreatic ductal adenocarcinoma is the deadliest of all common cancers. The reasons for this are the advanced cancer stage by the time symptoms are noted and the occult presence of micrometastases in the liver and elsewhere at the time of initial surgical treatment. In addition, systemic therapy with chemotherapy rarely...
- N Engl J Med 2022; 386:2112-2119
A 71-year-old woman with progressive pancreatic adenocarcinoma containing a mutated KRAS oncogene was given adoptive cellular therapy of her own T cells that had been altered to express two different T-cell receptors specific for her HLA type and the mutated KRAS in the tumor. Six months...
- N Engl J Med 2022; 386:1998-2010
In two small series of patients with myelodysplastic syndrome, the use of demethylating-agent therapy that was aimed at inducing cell differentiation resulted in induction of expression of the SALL4 oncogene in more than 30% of patients, and such expression was associated with a poorer natural history.
- N Engl J Med 2022; 386:1922-1931
Childhood brain tumors were previously classified by histologic appearance and location. A new classification includes genetic changes, which have prognostic significance and may lead to therapeutic targets. This review focuses on pediatric gliomas, ependymomas, and medulloblastomas.
- N Engl J Med 2022; 386:1453-1461
An 80-year-old woman was admitted with pancytopenia. Five weeks earlier, nausea, vomiting, diarrhea, chills, and fever had developed. CT revealed bilateral pelvic masses; examination of a peripheral-blood smear revealed schistocytes, anisocytosis, and a low platelet count. A diagnostic test was performed, and management decisions were made.
- N Engl J Med 2022; 386:992-994
Genetic landscaping and T cells are all the rage when it comes to tumor biology. Put them together and you get a comprehensive view of the T cell in the context of different types of cancer. The authors of this commentary provide a framework for a study of the RNAome...
- N Engl J Med 2022; 386:596-598
Clonal hematopoiesis of indeterminate potential (CHIP) is relatively common in older persons and is a risk factor for malignant blood conditions and cardiovascular disease. A recent study of a zebrafish model provides insight into how CHIP may evolve and implicates a positive feedback cycle.
- N Engl J Med 2021; 385:2059-2065
Pacak–Zhuang syndrome is an inherited tumor-predisposition disorder characterized by polycythemia and paragangliomas. A patient with this disorder had polycythemia, headache, hypertension, and norepinephrine-secreting paragangliomas. She had activating mutations in HIF2A. Use of belzutifan, a HIF2α inhibitor, led to paraganglioma regression, normalized hemoglobin levels, and symptom resolution.
- N Engl J Med 2021; 385:2036-2046
The cause of von Hippel–Lindau disease is excess activity of the HIF-2α pathway. A total of 61 patients with renal cell carcinoma and other proliferative manifestations of the hypoxia-induced signaling pathway received belzutifan, which inhibits the HIF-2α pathway. Nearly half the patients with renal cell carcinoma had a response to...
- N Engl J Med 2021; 385:2090-2091
Patients with von Hippel–Lindau (VHL) disease, a rare autosomal dominant inherited disease,1 have a shorter life expectancy than the general population.2,3 A prospective analysis involving 128 patients in Italy showed that mortality among persons in the VHL population who were between 25 and 64 years of...
- N Engl J Med 2021; 385:1807-1809
A growing body of evidence supports aberrant splicing as both a cause and a potential Achilles’ heel of cancers, especially when it comes to the effects of immune-checkpoint inhibitors.
- N Engl J Med 2021; 385:834-843
A 49-year-old man was evaluated because of relapsed acute myeloid leukemia that occurred 14 months after the initial diagnosis and treatment. Molecular genetic profiling at the time of relapse identified a new internal tandem duplication mutation in FLT3 (FLT3 -ITD). A bone marrow biopsy was performed, and...