CD38 is a myeloid antigen present both on the cell membrane and in the intracellular compartment of the cell. Its occurrence is often enhanced in cancer cells, thus making it a potential target in anticancer therapy. Daratumumab and isatuximab already received FDA approval, and novel agents such as MOR202, TAK079 and TNB-738 undergo clinical trials. Also, novel therapeutics such as SAR442085 aim to outrank the older antibodies against CD38. Multiple myeloma and immunoglobulin light-chain amyloidosis may be effectively treated with anti-CD38 immunotherapy. Its role in other hematological malignancies is also important concerning both diagnostic process and potential treatment in the future. Aside from the hematological malignancies, CD38 remains a potential target in gastrointestinal, neurological and pulmonary system disorders. Due to the strong interaction of CD38 with TCR and CD16 on T cells, it may also serve as the biomarker in transplant rejection in renal transplant patients. Besides, CD38 finds its role outside oncology in systemic lupus erythematosus and collagen-induced arthritis. CD38 plays an important role in viral infections, including AIDS and COVID-19. Most of the undergoing clinical trials focus on the use of anti-CD38 antibodies in the therapy of multiple myeloma, CD19- B-cell malignancies, and NK cell lymphomas. This review focuses on targeting CD38 in cancer and non-cancerous diseases using antibodies, cell-based therapies and CD38 inhibitors. We also provide a summary of current clinical trials targeting CD38.
Ataxia-telangiectasia (AT) is a multisystemic neurodegenerative inborn error of immunity (IEI) characterized by DNA repair defect, chromosomal instability, and hypersensitivity to ionizing radiation. Impaired DNA double-strand break repair determines a high risk of developing hematological malignancies, especially lymphoproliferative diseases. Poor response to treatment, excessive chemotherapy toxicities, and the need for avoiding exposure to ionizing radiation make the successful clinical management of patients with AT challenging for oncologists. We describe the favorable outcome of the LBCL with IRF4 rearrangement at stage III in a 7-year-old female patient diagnosed with AT. The patient was treated according to the B-HR arm of the INTER-B-NHL-COP 2010 protocol, including the administration of rituximab, cyclophosphamide, methotrexate, prednisone, etc. She presented excessive treatment toxicities despite individually reduced doses of methotrexate and cyclophosphamide. However, in the MRI there was no significant reduction in pathologic lymph nodes after three immunochemotherapy courses. Therefore, a lymph node biopsy was taken. Its subsequent histopathological examination revealed tuberculosis-like changes, though tuberculosis suspicion was excluded. After two following immunochemotherapy courses, PET-CT confirmed complete remission. From March 2022 onwards, the patient has remained in remission under the care of the outpatient children’s oncology clinic.
Gastrointestinal stromal tumor is the most common mesenchymal neoplasm of the gastrointestinal tract, usually found in elderly adults. It is infrequent among pediatric patients and usually differs biologically from adult-type diseases presenting mutations of KIT and PDGFR genes. In this population, more frequent is the wild-type GIST possessing SDH, TRK, RAS, NF1 mutations, among others. Both tumor types require individualized treatment with kinase inhibitors that are still being tested in the pediatric population due to the different neoplasm biology. We review the latest updates to the management of pediatric gastrointestinal tumors with a particular focus on the advances in molecular biology of the disease that enables the definition of possible resistance. Emerging treatment with kinase inhibitors that could serve as targeted therapy is discussed, especially with multikinase inhibitors of higher generation, the effectiveness of which has already been confirmed in the adult population.
BACKGROUND Google Trends (GT) is a freely-available tool presenting Google search statistics. GT is becoming a feasible tool to analyze the interest of Google users in different health phenomena. However, there are a few reviews on GT, and none has contributed specifically to oncology. OBJECTIVE We aimed to systematically characterize studies related to oncology using GT to describe its utilities and biases. METHODS We included all studies utilizing GT to analyze Google searches related to malignancies. We excluded studies written in non-English. The search was done on the PubMed engine on 1st August 2022. We used the following search input: "Google trends" AND ("oncology" OR "cancer" OR "malignancy" OR "tumor" OR "lymphoma" OR "multiple myeloma" OR "leukemia"). We analyzed the following sources of bias: 1) using search terms instead of topics, 2) lack of confrontation with real-world data, and 3) absence of a sensitivity analysis. We performed descriptive statistics. RESULTS A total of n=85 articles were included. We classified n=19 (22.4%) studies as related to prophylaxis, n=17 (20.0%) as an awareness event, n=9 (10.6%) as celebrity-related, n=11 (12.9%) related to COVID-19 and n=40 (47.1%) as others. The most frequently analyzed cancers were: breast (n=28), prostate (n=26), lung, and colorectal (both: n=18). n=79 (92.9%) of the studies provided all search input details to reproduce their results, and n=34 (40%.0) studies confronted GT statistics with real-world data. Authors of only n = 9 (10.6%) studies performed sensitivity analysis. CONCLUSIONS The studies in this systematic review varied regarding topics, search strategy, and statistical methods. Most researchers provided reproducible search inputs, but many studies lacked sensitivity analysis.Scientists using GT for medical research should ensure the quality of studies by 1) providing a search strategy to reproduce results, 2) preferring using topics instead of search terms, and 3) performing robust statistical calculations and sensitivity analysis.
Background The internet is a primary source of health information for patients, supplementing physician care. Google Trends (GT), a popular tool, allows the exploration of public interest in health-related phenomena. Despite the growing volume of GT studies, none have focused explicitly on oncology, creating a need for a systematic review to bridge this gap. Objective We aimed to systematically characterize studies related to oncology using GT to describe its utilities and biases. Methods We included all studies that used GT to analyze Google searches related to malignancies. We excluded studies written in languages other than English. The search was performed using the PubMed engine on August 1, 2022. We used the following search input: “Google trends” AND (“oncology” OR “cancer” or “malignancy” OR “tumor” OR “lymphoma” OR “multiple myeloma” OR “leukemia”). We analyzed sources of bias that included using search terms instead of topics, lack of confrontation of GT statistics with real-world data, and absence of sensitivity analysis. We performed descriptive statistics. Results A total of 85 articles were included. The first study using GT for oncology research was published in 2013, and since then, the number of publications has increased annually. The studies were categorized as follows: 22% (19/85) were related to prophylaxis, 20% (17/85) pertained to awareness events, 11% (9/85) were celebrity-related, 13% (11/85) were related to COVID-19, and 47% (40/85) fell into other categories. The most frequently analyzed cancers were breast (n=28), prostate (n=26), lung (n=18), and colorectal cancers (n=18). We discovered that of the 85 studies, 17 (20%) acknowledged using GT topics instead of search terms, 79 (93%) disclosed all search input details necessary for replicating their results, and 34 (40%) compared GT statistics with real-world data. The most prevalent methods for analyzing the GT data were correlation analysis (55/85, 65%) and peak analysis (43/85, 51%). The authors of only 11% (9/85) of the studies performed a sensitivity analysis. Conclusions The number of studies related to oncology using GT data has increased annually. The studies included in this systematic review demonstrate a variety of concerning topics, search strategies, and statistical methodologies. The most frequently analyzed cancers were breast, prostate, lung, colorectal, skin, and cervical cancers, potentially reflecting their prevalence in the population or public interest. Although most researchers provided reproducible search inputs, only one-fifth used GT topics instead of search terms, and many studies lacked a sensitivity analysis. Scientists using GT for medical research should ensure the quality of studies by providing a transparent search strategy to reproduce results, preferring to use topics over search terms, and performing robust statistical calculations coupled with sensitivity analysis.
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