Abhijit Patel, MD, PhD
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Appointments
Titles
Medical Director, Lawrence & Memorial Cancer Care Center in Waterford, Therapeutic Radiology
Contact Info
Therapeutic Radiology
PO Box 208040
New Haven, CT 06520-8040
United States
Appointments
Titles
Medical Director, Lawrence & Memorial Cancer Care Center in Waterford, Therapeutic Radiology
Contact Info
Therapeutic Radiology
PO Box 208040
New Haven, CT 06520-8040
United States
Appointments
Titles
Medical Director, Lawrence & Memorial Cancer Care Center in Waterford, Therapeutic Radiology
Contact Info
Therapeutic Radiology
PO Box 208040
New Haven, CT 06520-8040
United States
About
Titles
Associate Professor of Therapeutic Radiology
Medical Director, Lawrence & Memorial Cancer Care Center in Waterford, Therapeutic RadiologyAppointments
Therapeutic Radiology
Associate Professor on TermPrimary
Other Departments & Organizations
Education & Training
- Residency
- Harvard Radiation Oncology (2008)
- Postdoctoral Research
- HHMI, Massachusetts General Hospital (2008)
- Internship
- Memorial Sloan-Kettering Cancer Center (2004)
- MD
- Yale University School of Medicine (2003)
- PhD
- Yale University Graduate School, Molecular Biophysics and Biochemistry (2002)
- MS
- Yale College, Chemistry (1995)
- BS
- Yale College, Chemistry (1995)
Research
Overview
The release of nucleic acids from tumors into the bloodstream has been well documented in patients with various types of cancer. Recent technological advances are making it possible to analyze these circulating DNA and RNA fragments in ways that are proving to be clinically informative. To better understand the biological features and limitations of circulating nucleic acids, further improvements in assay methods are still needed. Our research efforts are focused on developing more robust analytical methods and on establishing the clinical utility of these methods.
ASSAY DEVELOPMENT:
Circulating tumor DNA
Tumor-derived DNA fragments in the circulation can be distinguished based on the presence of cancer-specific mutations. However, these mutant DNA copies are often obscured by a relative excess of wild-type background DNA in the plasma. In patients with early stage tumors or minimal residual disease following treatment, the fraction of mutant tumor-derived DNA in plasma can be well below 1 in 1,000. Detection of such low-abundance DNA variants poses a significant technical challenge, especially if one has no prior knowledge of the tumor’s mutation profile. We have developed methods to enrich mutation-prone regions of plasma DNA by highly multiplexed PCR. We use next-generation DNA sequencing technologies to oversample thousands of copies of these mutation-prone genomic regions, allowing rare sequence variants to be identified and enumerated. However, the sensitivity of this approach is limited by sequencer errors and PCR misincorporations, both of which might be mistaken for true mutant copies. To overcome this limitation, we have devised molecular and computational error-suppression strategies that enable ultrasensitive detection of rare mutant copies with broad mutation coverage.
High-throughput RNA profiling
Tumors are known to shed RNA molecules into blood. These circulating RNAs are surprisingly stable when bound to serum proteins or when encapsulated within tiny vesicles called exosomes. Such tumor-derived RNAs are showing great promise as biomarkers for cancer diagnosis and treatment monitoring. To facilitate analysis of RNAs from many patient samples in a high-throughput, low-cost manner, we have developed a method called META RNA profiling (for “modular early-tagged amplification”). The method is able to quantify a broad panel of microRNAs or messenger RNAs simultaneously across a large number of samples. It uses a next-generation sequencing readout, but demands far less sequence depth than existing digital RNA profiling approaches. An up-front quantitative tagging scheme allows all samples to be pooled, simplifying downstream processing steps and reducing inter-sample variability. While this approach can be applied to RNA samples derived from a variety of biological sources, we are using it as a tool to analyze gene expression in tumors and in clinical biofluids.
CLINICAL APPLICATIONS:
Liquid biopsy
The ability to sample tumor-derived nucleic acids in blood provides an opportunity to analyze a tumor’s mutations and gene expression signatures without requiring an invasive procedure to obtain a tissue specimen. Such information can be used to personalize cancer therapy, as drug choices are often guided by knowledge of a tumor’s genomic profile. Moreover, because tumors are known to be heterogeneous, a tissue biopsy taken from a single tumor site might miss critical genetic features present in other metastatic sites within the same patient. Because blood contains a sampling of nucleic acids derived from all tumors in the body, it is likely to enable a more comprehensive assessment of genomic heterogeneity. We are testing these concepts using clinical samples from patients with various types of cancer.
Assessment of treatment response
As is true for many protein biomarkers, quantitative changes in the levels of circulating nucleic acids appear to be correlated with treatment response. This may prove useful in assessing the response of tumors for which good serum protein markers are not available. We are also investigating whether unique aspects of nucleic acid specificity and kinetics can be exploited to complement information obtained from protein markers.
Emergence of treatment resistance
Genomic profiles of tumors are known to evolve over time. This can be especially important when a therapy leads to the selective proliferation of tumor cell populations containing mutations that confer treatment resistance. Therapy can be modified if the emergence of resistant clones is documented by repeating a biopsy, but such invasive procedures can be risky and impractical. We are evaluating whether nucleic acids in blood can be used to noninvasively track genomic and transcriptomic changes in tumors over time. Might we be able to predict treatment resistance before it becomes clinically evident?
Early detection of new and recurrent cancer
It has long been one of the grand challenges of oncology to detect tumors at their earliest stages, when treatment is more likely to be curative. However, efforts to develop blood tests for early cancer detection have had limited success because of the difficulty in identifying serum protein biomarkers that are sufficiently cancer-specific. Circulating tumor DNA may be a better-suited marker for cancer screening because tumor-specific somatic mutations can be used to distinguish tumor-derived DNA molecules. Since cancer-associated mutations should rarely be found in the plasma of healthy individuals, false-positive results are expected to be extremely uncommon. Furthermore, because there is no physiologic background, a small amount of mutant DNA released from an early-stage tumor should be detectable if the technical background of the assay can be minimized. Similar principles apply to the detection of small amounts of residual or recurrent disease following curative-intent therapy. We are keenly interested in evaluating whether our ultrasensitive ctDNA assay can be used for early detection of new or recurrent tumors.
Medical Subject Headings (MeSH)
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Scott Gettinger, MD
Henry S. Park, MD, MPH
Jill Lacy, MD
Joan Steitz, PhD
Roy S. Herbst, MD, PhD
Sarah Goldberg, MD, MPH
Publications
2024
Single-stranded pre-methylated 5mC adapters uncover the methylation profile of plasma ultrashort Single-stranded cell-free DNA
Cheng J, Swarup N, Morselli M, Huang W, Aziz M, Caggiano C, Kordi M, Patel A, Chia D, Kim Y, Li F, Wei F, Zaitlen N, Krysan K, Dubinett S, Pellegrini M, Wong D. Single-stranded pre-methylated 5mC adapters uncover the methylation profile of plasma ultrashort Single-stranded cell-free DNA. Nucleic Acids Research 2024, 52: e50-e50. PMID: 38797520, PMCID: PMC11194076, DOI: 10.1093/nar/gkae276.Peer-Reviewed Original ResearchAltmetricConceptsTranscription start siteMethylation profilesCell-free DNAWhole-genome bisulfite sequencingCytosine methylation changesLevels of DNA methylationSingle-base resolutionUpstream transcription start siteBS-seqStart siteBisulfite sequencingCpG islandsDNA fragmentationBisulfite conversionMethylation changesDNA methylationBisulfite treatmentLarge DNAsMethylation analysisDNANon-cancer samplesBisulfiteFragmentsHemopoietic cellsMethylationCirculating Tumor DNA Dynamics Fail to Predict Efficacy of Poly(ADP-ribose) Polymerase/VEGFR Inhibition in Patients With Heavily Pretreated Advanced Solid Tumors.
Hu Y, Narayan A, Xu Y, Wolfe J, Vu D, Trinh T, Kantak C, Ivy S, Eder J, Deng Y, LoRusso P, Kim J, Patel A. Circulating Tumor DNA Dynamics Fail to Predict Efficacy of Poly(ADP-ribose) Polymerase/VEGFR Inhibition in Patients With Heavily Pretreated Advanced Solid Tumors. JCO Precision Oncology 2024, 8: e2300289. PMID: 38412387, PMCID: PMC10914240, DOI: 10.1200/po.23.00289.Peer-Reviewed Original ResearchAltmetricMeSH Keywords and ConceptsConceptsCell-free circulating tumor DNANon-small-cell lung cancerSmall-cell lung cancerTriple-negative breast cancerPancreatic ductal adenocarcinomaAdvanced solid tumorsVariant allele fractionRadiographic responseOverall survivalCombination therapySolid tumorsCtDNA levelsLung cancerPretreated advanced solid tumorsDays of combination therapyMetastatic pancreatic ductal adenocarcinomaResponse to anticancer therapyAssociated with disease progressionProgression-free survivalPlasma samplesLead-inPoly(ADP-riboseInferior OSTumor DNASurvival outcomes
2023
Extrinsic and intrinsic preanalytical variables affecting liquid biopsy in cancer.
Batool SM, Hsia T, Beecroft A, Lewis B, Ekanayake E, Rosenfeld Y, Escobedo AK, Gamblin AS, Rawal S, Cote RJ, Watson M, Wong DTW, Patel AA, Skog J, Papadopoulos N, Bettegowda C, Castro CM, Lee H, Srivastava S, Carter BS, Balaj L. Extrinsic and intrinsic preanalytical variables affecting liquid biopsy in cancer. Cell Rep Med 2023, 4: 101196. PMID: 37725979, DOI: 10.1016/j.xcrm.2023.101196.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsThe Liquid Biopsy Consortium: Challenges and opportunities for early cancer detection and monitoring
Batool S, Yekula A, Khanna P, Hsia T, Gamblin A, Ekanayake E, Escobedo A, You D, Castro C, Im H, Kilic T, Garlin M, Skog J, Dinulescu D, Dudley J, Agrawal N, Cheng J, Abtin F, Aberle D, Chia D, Elashoff D, Grognan T, Krysan K, Oh S, Strom C, Tu M, Wei F, Xian R, Skates S, Zhang D, Trinh T, Watson M, Aft R, Rawal S, Agarwal A, Kesmodel S, Yang C, Shen C, Hochberg F, Wong D, Patel A, Papadopoulos N, Bettegowda C, Cote R, Srivastava S, Lee H, Carter B, Balaj L. The Liquid Biopsy Consortium: Challenges and opportunities for early cancer detection and monitoring. Cell Reports Medicine 2023, 4: 101198. PMID: 37716353, PMCID: PMC10591039, DOI: 10.1016/j.xcrm.2023.101198.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsCitationsAltmetricMeSH Keywords and ConceptsctDNA and Lung Cancer
Cheng J, Hu Y, Wong D, Patel A. ctDNA and Lung Cancer. Current Cancer Research 2023, 511-537. DOI: 10.1007/978-3-031-22903-9_20.ChaptersConceptsCell-free DNALung cancerNon-small cell lung cancerCell lung cancerMinimal residual diseaseResidual diseasePleural fluidImportant clinical applicationsClinical utilityTreatment selectionEarly cancer detectionPhysiologic underpinningsClinical modelTherapy monitoringClinical applicationCancerCancer detection
2022
Platelet-derived TLT-1 promotes tumor progression by suppressing CD8+ T cells
Tyagi T, Jain K, Yarovinsky TO, Chiorazzi M, Du J, Castro C, Griffin J, Korde A, Martin KA, Takyar SS, Flavell RA, Patel AA, Hwa J. Platelet-derived TLT-1 promotes tumor progression by suppressing CD8+ T cells. Journal Of Experimental Medicine 2022, 220: e20212218. PMID: 36305874, PMCID: PMC9814191, DOI: 10.1084/jem.20212218.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsCD8 T cellsT cellsTLT-1Non-small cell lung cancer patientsCell lung cancer patientsTREM-like transcript-1Tumor immunosuppressive mechanismsT cell suppressionLung cancer patientsPatient T cellsNF-κB pathwayPatient-derived tumorsDistinct activation phenotypesNSCLC patientsImmunosuppressive mechanismsSyngeneic tumorsHumanized miceImmunoregulatory rolePrognostic significanceImmunocompetent miceCancer patientsCell suppressionActivation phenotypeReduced tumorTumor growthDirect capture and sequencing reveal ultra-short single-stranded DNA in biofluids
Cheng LY, Dai P, Wu LR, Patel AA, Zhang DY. Direct capture and sequencing reveal ultra-short single-stranded DNA in biofluids. IScience 2022, 25: 105046. PMID: 36147958, PMCID: PMC9486625, DOI: 10.1016/j.isci.2022.105046.Peer-Reviewed Original ResearchCitationsAltmetricLimitations and opportunities of technologies for the analysis of cell-free DNA in cancer diagnostics
Song P, Wu LR, Yan YH, Zhang JX, Chu T, Kwong LN, Patel AA, Zhang DY. Limitations and opportunities of technologies for the analysis of cell-free DNA in cancer diagnostics. Nature Biomedical Engineering 2022, 6: 232-245. PMID: 35102279, PMCID: PMC9336539, DOI: 10.1038/s41551-021-00837-3.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and Concepts
2021
Selective multiplexed enrichment for the detection and quantitation of low-fraction DNA variants via low-depth sequencing
Song P, Chen SX, Yan YH, Pinto A, Cheng LY, Dai P, Patel AA, Zhang DY. Selective multiplexed enrichment for the detection and quantitation of low-fraction DNA variants via low-depth sequencing. Nature Biomedical Engineering 2021, 5: 690-701. PMID: 33941896, PMCID: PMC9631981, DOI: 10.1038/s41551-021-00713-0.Peer-Reviewed Original ResearchCitationsAltmetricTumor DNA Mutations From Intraparenchymal Brain Metastases Are Detectable in CSF
Cheok SK, Narayan A, Arnal-Estape A, Gettinger S, Goldberg SB, Kluger HM, Nguyen D, Patel A, Chiang V. Tumor DNA Mutations From Intraparenchymal Brain Metastases Are Detectable in CSF. JCO Precision Oncology 2021, 5: 163-172. PMID: 34250381, PMCID: PMC8232069, DOI: 10.1200/po.20.00292.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsIntraparenchymal brain metastasesBrain metastasesCell-free DNAExtracranial tumorsBrain metastasis tissuesProgressive brain metastasesThird of patientsNormal pressure hydrocephalusTumor DNA mutationsPrimary cancer typeAnalysis of CSFSamples of CSFLeptomeningeal diseaseEffective surrogate markerBrain biopsyPressure hydrocephalusLumbar punctureSurrogate markerCancer-associated genesMetastasis tissuesPatientsMetastasisDiscordant responsesRenal cellsGenomic profiling
Clinical Trials
Current Trials
Parallel Phase III Randomized Trials for High Risk Prostate Cancer Evaluating De-Intensification for Lower Genomic Risk and Intensification of Concurrent Therapy for Higher Genomic Risk With Radiation (PREDICT-RT*)
HIC ID2000032279RoleSub InvestigatorPrimary Completion Date12/31/2033Recruiting ParticipantsMRI Brain Surveillance Alone Versus MRI Surveillance and Prophylactic Cranial Irradiation (PCI): A Randomized Phase III Trial in Small-Cell Lung Cancer (MAVERICK)
HIC ID2000027403RoleSub InvestigatorPrimary Completion Date11/15/2025Recruiting ParticipantsPhase IB/II Trial Of Dose-Deescalated 3-Fraction Stereotactic Body Radiotherapy For Centrally Located Lung Cancer
HIC ID2000025868RoleSub InvestigatorPrimary Completion Date01/31/2030Recruiting ParticipantsDetermining Mechanisms of Sensitivity and Resistance to Anti-Cancer Therapy for Advanced Lung Cancer
HIC ID1603017333RoleSub InvestigatorPrimary Completion Date06/20/2026Recruiting ParticipantsPeripheral Blood Profiling to Screen Patients for Lung Cancer or Lung Cancer Recurrence
HIC ID1407014379RoleSub InvestigatorPrimary Completion Date09/30/2024Recruiting Participants
Academic Achievements and Community Involvement
honor Lungevity Foundation Early Detection Award
National AwardDetails08/12/2015United Stateshonor Tina's Wish Foundation Research Award
National AwardDetails08/12/2015United Stateshonor ASTRO Junior Faculty Career Research Training Award
UnknownAmerican Society for Radiation OncologyDetails07/01/2011United Stateshonor Brozman Foundation Fellowship
UnknownDetails01/01/2011United Stateshonor American Cancer Society Institutional Research Grant
UnknownDetails07/01/2010United States
Clinical Care
Overview
Clinical Specialties
Fact Sheets
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Board Certifications
Radiation Oncology
- Certification Organization
- AB of Radiology
- Original Certification Date
- 2009
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- June 01, 2024
Accolades, Awards & Honors
- January 11, 2023
Discoveries & Impact (January 2023)
- January 04, 2022
Prostate and Urologic Cancers Clinic at the Smilow Cancer Hospital Care Center in Waterford
- June 23, 2021
Smilow Cancer Hospital Care Center at Waterford physician makes ‘Top Docs’ list in Connecticut
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Therapeutic Radiology
PO Box 208040
New Haven, CT 06520-8040
United States
Locations
Hunter Building
Academic Office
15 York Street, Ste HRT 213C
New Haven, CT 06510
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Are You a Patient? View this doctor's clinical profile on the Yale Medicine website for information about the services we offer and making an appointment.