Anish Thomas
National Institutes of Health
CancerInternal medicinePathologyOncologyImmunologyLung cancerThymic carcinomaChemotherapyMesothelinMesotheliomaImmunotherapyThymomaAdenocarcinomaTargeted therapyNon small cellCancer researchClinical trialMedicineBiologyImmune system
Publications 181
PURPOSE Although several ATR inhibitors are in development, there are unresolved questions regarding their differential potency, molecular signatures of cancer patients for predicting activity and most effective therapeutic combinations. Here, we elucidate how to improve ATR-based chemotherapy with the newly developed ATR inhibitor, M4344 using in vitro and in vivo models. EXPERIMENTAL DESIGN The potency of M4344 was compared with the clinically developed ATR inhibitors BAY1895344, berzosertib, ...
#1Anish Thomas (NIH: National Institutes of Health)H-Index: 36
#2Nobuyuki Takahashi (NIH: National Institutes of Health)H-Index: 10
Last. Craig J. Thomas (NIH: National Institutes of Health)H-Index: 69
view all 41 authors...
Small cell neuroendocrine cancers (SCNCs) are recalcitrant cancers arising from diverse primary sites that lack effective treatments. Using chemical genetic screens, we identified inhibition of ataxia telangiectasia and rad3 related (ATR), the primary activator of the replication stress response, and topoisomerase I (TOP1), nuclear enzyme that suppresses genomic instability, as synergistically cytotoxic in small cell lung cancer (SCLC). In a proof-of-concept study, we combined M6620 (berzosertib...
2 CitationsSource
#1Camille TlemsaniH-Index: 2
#2Nobuyuki TakahashiH-Index: 21
Last. Anish ThomasH-Index: 36
view all 25 authors...
Because tobacco is a potent carcinogen, secondary causes of lung cancer are often diminished in perceived importance. To assess the extent of inherited susceptibility to small cell lung cancer (SCLC), the most lethal type of lung cancer, we sequenced germline exomes of 87 patients (77 SCLC and 10 extrapulmonary small cell) and considered 607 genes, discovering 42 deleterious variants in 35 cancer-predisposition genes among 43.7% of patients. These findings were validated in an independent cohort...
#1Raffit HassanH-Index: 58
#2Christine Alewine (LMB: Laboratory of Molecular Biology)H-Index: 10
Last. Ira Pastan (LMB: Laboratory of Molecular Biology)H-Index: 191
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Background LMB-100 is an antibody-toxin conjugate with an antimesothelin Fab linked to a 24-kilodalton portion of Pseudomonas exotoxin A with mutations that decrease immunogenicity. The objective of the current first-in-human phase 1 study was to determine the maximum tolerated dose (MTD) and safety in patients with advanced solid tumors expressing mesothelin. Methods Cohorts of 1 to 7 patients received intravenous LMB-100 at 7 dose levels from 40 µg/kg to 250 µg/kg intravenously on days 1, 3, a...
4 CitationsSource
#1James C. Reynolds (NIH: National Institutes of Health)H-Index: 71
#2Roberto Maass-Moreno (NIH: National Institutes of Health)H-Index: 7
Last. Raffit HassanH-Index: 58
view all 7 authors...
Cancer Survival is related to tumor volume. FDG PET measurement of tumor volume holds promise but is not yet a clinical tool. Measurements come in two forms: the total lesion volume (TLV) based on the number of voxels in the tumor and secondly the total lesion glycolysis (TLG) which is the TLV multiplied by the average SUL per voxel of the tumor (SUL is the standardize uptake value normalized for lean mass). In this study we measured tumor volume in patients with malignant pleural mesothelioma (...
1 CitationsSource
#1Camille TlemsaniH-Index: 2
#2Lorinc PongorH-Index: 6
Last. Yves PommierH-Index: 146
view all 19 authors...
Summary CellMiner-SCLC ( ) integrates drug sensitivity and genomic data, including high-resolution methylome and transcriptome from 118 patient-derived small cell lung cancer (SCLC) cell lines, providing a resource for research into this “recalcitrant cancer.” We demonstrate the reproducibility and stability of data from multiple sources and validate the SCLC consensus nomenclature on the basis of expression of master transcription factors NEUROD1, ...
8 CitationsSource
#1Nobuyuki TakahashiH-Index: 21
#2Vinodh N. RajapakseH-Index: 16
Last. Anish ThomasH-Index: 36
view all 13 authors...
Mismatch repair-deficient (dMMR) cancers generate a substantial number of immunogenic neoantigens, rendering them sensitive to immunotherapy. Yet, there is considerable variability in responses, and roughly one-half of dMMR cancers are refractory to immunotherapy. Here we study a patient with dMMR lung cancer refractory to immunotherapy. The tumor exhibited typical dMMR molecular features, including exceptionally high frameshift insertions and deletions (indels). Despite the treatment inducing a...
#1Julius StraussH-Index: 11
#2Arun RajanH-Index: 30
Last. James L. GulleyH-Index: 10
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#1Keith T. Schmidt (NIH: National Institutes of Health)H-Index: 5
#2Alwin D. R. Huitema (UU: Utrecht University)H-Index: 66
Last. William D. Figg (NIH: National Institutes of Health)H-Index: 2
view all 11 authors...
NLG207 (formerly CRLX101) is a nanoparticle–drug conjugate (NDC) of the potent topoisomerase I inhibitor, camptothecin (CPT). The present study sought to characterize the complex pharmacokinetics (PK) of NLG207 and better describe CPT release from nanoparticles using a population PK (popPK) model. From 27 patients enrolled on two phase II clinical trials (NCT02769962 and NCT03531827), dense sampling was performed up to 48 h post-administration of NLG207 during cycle one and six of treatment; sam...
1 CitationsSource