Assistant Clinical Professor Division of Hematology/Oncology Department of Medicine
Biography
Dr. Blakely is a medical oncologist specializing in the treatment of lung cancer. He received his Bachelor of Science degree in Molecular and Cellular Biology from the University of Washington and attended the Perelman School of Medicine at the University of Pennsylvania in the Medical Scientist Training Program. He completed his Internal Medicine residency at the Hospital of the University of Pennsylvania and trained as a clinical fellow in Medical Oncology at UCSF. His research focuses on understanding the cellular and molecular mechanisms underlying lung cancer resistance to EGFR-, and ALK-targeted therapies, and identifying new targets for molecular-directed therapies. His goal is to translate laboratory-based findings into new treatments for lung cancer patients.
Related Conditions: Non-Small Cell Lung Cancer, Small Cell Carcinoma, Lung Cancer, Lung Tumor| Start Date: | End Date:
Research Narrative
The primary focus of my research is to translate laboratory-based findings into novel investigator sponsored trials that aim to assess the safety and efficacy of rationally designed targeted therapies for lung cancer patients.
My goals are to: 1) define how TKI resistance pathways evolve at the tumor genome, transcriptome and molecular signaling levels within lung cancers and to translate these findings into novel prognostic and predictive biomarkers that may predict TKI resistance before it occurs; 2) develop investigator sponsored clinical trials to test rational companion therapies that can prevent, delay, or overcome TKI resistance, 3) develop investigator sponsored clinical trials to target recently identified oncogenic pathways, outside of EGFR and ALK, that drive NSCLC; and 4) establish a cohort of patient-derived xenograft (PDX) mice to foster research that aims to further understand the molecular mechanisms of response and resistance to TKI therapies in lung cancer
Research Interests
EGFR-mutant lung cancer
ALK-rearranged lung cancer
ROS1-rearranged lung cancer
Mechanisms of resistance to targeted therapies
Publications
MOST RECENT PUBLICATIONS FROM A TOTAL OF 57
CTLA4 blockade abrogates KEAP1/STK11-related resistance to PD-(L)1 inhibitors.
Skoulidis F, Araujo HA, Do MT, Qian Y, Sun X, Cobo AG, Le JT, Montesion M, Palmer R, Jahchan N, Juan JM, Min C, Yu Y, Pan X, Arbour KC, Vokes N, Schmidt ST, Molkentine D, Owen DH, Memmott R, Patil PD, Marmarelis ME, Awad MM, Murray JC, Hellyer JA, Gainor JF, Dimou A, Bestvina CM, Shu CA, Riess JW, Blakely CM, Pecot CV, Mezquita L, Tabbó F, Scheffler M, Digumarthy S, Mooradian MJ, Sacher AG, Lau SCM, Saltos AN, Rotow J, Johnson RP, Liu C, Stewart T, Goldberg SB, Killam J, Walther Z, Schalper K, Davies KD, Woodcock MG, Anagnostou V, Marrone KA, Forde PM, Ricciuti B, Venkatraman D, Van Allen EM, Cummings AL, Goldman JW, Shaish H, Kier M, Katz S, Aggarwal C, Ni Y, Azok JT, Segal J, Ritterhouse L, Neal JW, Lacroix L, Elamin YY, Negrao MV, Le X, Lam VK, Lewis WE, Kemp HN, Carter B, Roth JA, Swisher S, Lee R, Zhou T, Poteete A, Kong Y, Takehara T, Paula AG, Parra Cuentas ER, Behrens C, Wistuba II, Zhang J, Blumenschein GR, Gay C, Byers LA, Gibbons DL, Tsao A, Lee JJ, Bivona TG, Camidge DR, Gray JE, Lieghl N, Levy B, Brahmer JR, Garassino MC, Gandara DR, Garon EB, Rizvi NA, Scagliotti GV, Wolf J, Planchard D, Besse B, Herbst RS, Wakelee HA, Pennell NA, Shaw AT, Jänne PA, Carbone DP, Hellmann MD, Rudin CM, Albacker L, Mann H, Zhu Z, Lai Z, Stewart R, Peters S, Johnson ML, Wong KK, Huang A, Winslow MM, Rosen MJ, Winters IP, Papadimitrakopoulou VA, Cascone T, Jewsbury P, Heymach JV| | PubMed
Neoadjuvant Osimertinib for the Treatment of Stage I-IIIA Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer: A Phase II Multicenter Study.
Blakely CM, Urisman A, Gubens MA, Mulvey CK, Allen GM, Shiboski SC, Rotow JK, Chakrabarti T, Kerr DL, Aredo JV, Bacaltos B, Gee M, Tan L, Jones KD, Devine WP, Doebele RC, Aisner DL, Patil T, Schenk EL, Bivona TG, Riess JW, Coleman M, Kratz JR, Jablons DM| | PubMed
Current Trial Report: A Multicenter Phase I/Ib study of Capmatinib Plus Trametinib in Patients With Metastatic Nonsmall Cell Lung Center Harboring MET Exon 14 Skipping Mutations and Other MET-Alterations.
Mixed responses to targeted therapy driven by chromosomal instability through p53 dysfunction and genome doubling.
Hobor S, Al Bakir M, Hiley CT, Skrzypski M, Frankell AM, Bakker B, Watkins TBK, Markovets A, Dry JR, Brown AP, van der Aart J, van den Bos H, Spierings D, Oukrif D, Novelli M, Chakrabarti T, Rabinowitz AH, Ait Hassou L, Litière S, Kerr DL, Tan L, Kelly G, Moore DA, Renshaw MJ, Venkatesan S, Hill W, Huebner A, Martínez-Ruiz C, Black JRM, Wu W, Angelova M, McGranahan N, Downward J, Chmielecki J, Barrett C, Litchfield K, Chew SK, Blakely CM, de Bruin EC, Foijer F, Vousden KH, Bivona TG, TRACERx consortium, Hynds RE, Kanu N, Zaccaria S, Grönroos E, Swanton C| | PubMed
Focal adhesion kinase-YAP signaling axis drives drug-tolerant persister cells and residual disease in lung cancer.
Haderk F, Chou YT, Cech L, Fernández-Méndez C, Yu J, Olivas V, Meraz IM, Barbosa Rabago D, Kerr DL, Gomez C, Allegakoen DV, Guan J, Shah KN, Herrington KA, Gbenedio OM, Nanjo S, Majidi M, Tamaki W, Pourmoghadam YK, Rotow JK, McCoach CE, Riess JW, Gutkind JS, Tang TT, Post L, Huang B, Santisteban P, Goodarzi H, Bandyopadhyay S, Kuo CJ, Roose JP, Wu W, Blakely CM, Roth JA, Bivona TG| | PubMed
PERCEPTION predicts patient response and resistance to treatment using single-cell transcriptomics of their tumors.
Sinha S, Vegesna R, Mukherjee S, Kammula AV, Dhruba SR, Wu W, Kerr DL, Nair NU, Jones MG, Yosef N, Stroganov OV, Grishagin I, Aldape KD, Blakely CM, Jiang P, Thomas CJ, Benes CH, Bivona TG, Schäffer AA, Ruppin E| | PubMed
The role of APOBEC3B in lung tumor evolution and targeted cancer therapy resistance.
Caswell DR, Gui P, Mayekar MK, Law EK, Pich O, Bailey C, Boumelha J, Kerr DL, Blakely CM, Manabe T, Martinez-Ruiz C, Bakker B, De Dios Palomino Villcas J, I Vokes N, Dietzen M, Angelova M, Gini B, Tamaki W, Allegakoen P, Wu W, Humpton TJ, Hill W, Tomaschko M, Lu WT, Haderk F, Al Bakir M, Nagano A, Gimeno-Valiente F, de Carné Trécesson S, Vendramin R, Barbè V, Mugabo M, Weeden CE, Rowan A, McCoach CE, Almeida B, Green M, Gomez C, Nanjo S, Barbosa D, Moore C, Przewrocka J, Black JRM, Grönroos E, Suarez-Bonnet A, Priestnall SL, Zverev C, Lighterness S, Cormack J, Olivas V, Cech L, Andrews T, Rule B, Jiao Y, Zhang X, Ashford P, Durfee C, Venkatesan S, Temiz NA, Tan L, Larson LK, Argyris PP, Brown WL, Yu EA, Rotow JK, Guha U, Roper N, Yu J, Vogel RI, Thomas NJ, Marra A, Selenica P, Yu H, Bakhoum SF, Chew SK, Reis-Filho JS, Jamal-Hanjani M, Vousden KH, McGranahan N, Van Allen EM, Kanu N, Harris RS, Downward J, Bivona TG, Swanton C| | PubMed
Comutations and KRASG12C Inhibitor Efficacy in Advanced NSCLC.
Negrao MV, Araujo HA, Lamberti G, Cooper AJ, Akhave NS, Zhou T, Delasos L, Hicks JK, Aldea M, Minuti G, Hines J, Aredo JV, Dennis MJ, Chakrabarti T, Scott SC, Bironzo P, Scheffler M, Christopoulos P, Stenzinger A, Riess JW, Kim SY, Goldberg SB, Li M, Wang Q, Qing Y, Ni Y, Do MT, Lee R, Ricciuti B, Alessi JV, Wang J, Resuli B, Landi L, Tseng SC, Nishino M, Digumarthy SR, Rinsurongkawong W, Rinsurongkawong V, Vaporciyan AA, Blumenschein GR, Zhang J, Owen DH, Blakely CM, Mountzios G, Shu CA, Bestvina CM, Garassino MC, Marrone KA, Gray JE, Patel SP, Cummings AL, Wakelee HA, Wolf J, Scagliotti GV, Cappuzzo F, Barlesi F, Patil PD, Drusbosky L, Gibbons DL, Meric-Bernstam F, Lee JJ, Heymach JV, Hong DS, Heist RS, Awad MM, Skoulidis F| | PubMed
Private Payer and Medicare Coverage Policies for Use of Circulating Tumor DNA Tests in Cancer Diagnostics and Treatment.
Douglas MP, Ragavan MV, Chen C, Kumar A, Gray SW, Blakely CM, Phillips KA| | PubMed
MRTX-500 Phase 2 Trial: Sitravatinib With Nivolumab in Patients With Nonsquamous NSCLC Progressing On or After Checkpoint Inhibitor Therapy or Chemotherapy.
He K, Berz D, Gadgeel SM, Iams WT, Bruno DS, Blakely CM, Spira AI, Patel MR, Waterhouse DM, Richards DA, Pham A, Jotte R, Hong DS, Garon EB, Traynor A, Olson P, Latven L, Yan X, Shazer R, Leal TA| | PubMed
CD73 Inhibitor Oleclumab Plus Osimertinib in Previously Treated Patients With Advanced T790M-Negative EGFR-Mutated NSCLC: A Brief Report.
Kim DW, Kim SW, Camidge DR, Shu CA, Marrone KA, Le X, Blakely CM, Park K, Chang GC, Patel SP, Kar G, Cooper ZA, Samadani R, Pluta M, Kumar R, Ramalingam S| | PubMed
Osimertinib in NSCLC With Atypical EGFR-Activating Mutations: A Retrospective Multicenter Study.
Ji J, Aredo JV, Piper-Vallillo A, Huppert L, Rotow JK, Husain H, Stewart S, Cobb R, Wakelee HA, Blakely CM, Wong ML, Gubens MA, Madani MH, Digumarthy SR, McCoach C, Piotrowska Z, Neal JW, Riess JW| | PubMed
Primary endpoints to assess the efficacy of novel therapeutic approaches in epidermal growth factor receptor-mutated, surgically resectable non-small cell lung cancer: A review.
Blakely CM, Weder W, Bubendorf L, He J, Majem M, Shyr Y, Chaft JE| | PubMed
Phase 1 Study of Ceritinib Combined With Trametinib in Patients With Advanced ALK- or ROS1-Positive NSCLC.
AXL and Error-Prone DNA Replication Confer Drug Resistance and Offer Strategies to Treat EGFR-Mutant Lung Cancer.
Noronha A, Belugali Nataraj N, Lee JS, Zhitomirsky B, Oren Y, Oster S, Lindzen M, Mukherjee S, Will R, Ghosh S, Simoni-Nieves A, Verma A, Chatterjee R, Borgoni S, Robinson W, Sinha S, Brandis A, Kerr DL, Wu W, Sekar A, Giri S, Chung Y, Drago-Garcia D, Danysh BP, Lauriola M, Fiorentino M, Ardizzoni A, Oren M, Blakely CM, Ezike J, Wiemann S, Parida L, Bivona TG, Aqeilan RI, Brugge JS, Regev A, Getz G, Ruppin E, Yarden Y| | PubMed
Deficiency of the splicing factor RBM10 limits EGFR inhibitor response in EGFR-mutant lung cancer.
Nanjo S, Wu W, Karachaliou N, Blakely CM, Suzuki J, Chou YT, Ali SM, Kerr DL, Olivas VR, Shue J, Rotow J, Mayekar MK, Haderk F, Chatterjee N, Urisman A, Yeo JC, Skanderup AJ, Tan AC, Tam WL, Arrieta O, Hosomichi K, Nishiyama A, Yano S, Kirichok Y, Tan DS, Rosell R, Okimoto RA, Bivona TG| | PubMed
Small-molecule targeted therapies induce dependence on DNA double-strand break repair in residual tumor cells.
Ali M, Lu M, Ang HX, Soderquist RS, Eyler CE, Hutchinson HM, Glass C, Bassil CF, Lopez OM, Kerr DL, Falcon CJ, Yu HA, Hata AN, Blakely CM, McCoach CE, Bivona TG, Wood KC| | PubMed
Small Cell Lung Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.
Ganti AKP, Loo BW, Bassetti M, Blakely C, Chiang A, D'Amico TA, D'Avella C, Dowlati A, Downey RJ, Edelman M, Florsheim C, Gold KA, Goldman JW, Grecula JC, Hann C, Iams W, Iyengar P, Kelly K, Khalil M, Koczywas M, Merritt RE, Mohindra N, Molina J, Moran C, Pokharel S, Puri S, Qin A, Rusthoven C, Sands J, Santana-Davila R, Shafique M, Waqar SN, Gregory KM, Hughes M| | PubMed
Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids.
Changes in older adults' life space during lung cancer treatment: A mixed methods cohort study.
Wong ML, Shi Y, Smith AK, Miaskowski C, Boscardin WJ, Cohen HJ, Lam V, Mazor M, Metzger L, Presley CJ, Williams GR, Loh KP, Ursem CJ, Friedlander TW, Blakely CM, Gubens MA, Allen G, Shumay D, Walter LC| | PubMed
Molecular Risk Stratification is Independent of EGFR Mutation Status in Identifying Early-Stage Non-Squamous Non-Small Cell Lung Cancer Patients at Risk for Recurrence and Likely to Benefit From Adjuvant Chemotherapy.
Woodard GA, Kratz JR, Haro G, Gubens MA, Blakely CM, Jones KD, Mann MJ, Jablons DM| | PubMed
Neoadjuvant osimertinib with/without chemotherapy versus chemotherapy alone for EGFR-mutated resectable non-small-cell lung cancer: NeoADAURA.
Tsuboi M, Weder W, Escriu C, Blakely C, He J, Dacic S, Yatabe Y, Zeng L, Walding A, Chaft JE| | PubMed
Efficacy and Safety of Rociletinib Versus Chemotherapy in Patients With EGFR-Mutated NSCLC: The Results of TIGER-3, a Phase 3 Randomized Study.
Yang JC, Reckamp KL, Kim YC, Novello S, Smit EF, Lee JS, Su WC, Akerley WL, Blakely CM, Groen HJM, Bazhenova L, Carcereny Costa E, Chiari R, Hsia TC, Golsorkhi T, Despain D, Shih D, Popat S, Wakelee H| | PubMed
Evaluation of a National Comprehensive Cancer Network Guidelines-Based Decision Support Tool in Patients With Non-Small Cell Lung Cancer: A Nonrandomized Clinical Trial.
Wu SY, Lazar AA, Gubens MA, Blakely CM, Gottschalk AR, Jablons DM, Jahan TM, Wang VEH, Dunbar TL, Wong ML, Chan JW, Guthrie W, Belkora J, Yom SS| | PubMed
Therapy-Induced Evolution of Human Lung Cancer Revealed by Single-Cell RNA Sequencing.
Maynard A, McCoach CE, Rotow JK, Harris L, Haderk F, Kerr DL, Yu EA, Schenk EL, Tan W, Zee A, Tan M, Gui P, Lea T, Wu W, Urisman A, Jones K, Sit R, Kolli PK, Seeley E, Gesthalter Y, Le DD, Yamauchi KA, Naeger DM, Bandyopadhyay S, Shah K, Cech L, Thomas NJ, Gupta A, Gonzalez M, Do H, Tan L, Bacaltos B, Gomez-Sjoberg R, Gubens M, Jahan T, Kratz JR, Jablons D, Neff N, Doebele RC, Weissman J, Blakely CM, Darmanis S, Bivona TG| | PubMed
Role of MPR as an Early Signal for Efficacy in Neoadjuvant Studies.
Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials.
Doebele RC, Drilon A, Paz-Ares L, Siena S, Shaw AT, Farago AF, Blakely CM, Seto T, Cho BC, Tosi D, Besse B, Chawla SP, Bazhenova L, Krauss JC, Chae YK, Barve M, Garrido-Laguna I, Liu SV, Conkling P, John T, Fakih M, Sigal D, Loong HH, Buchschacher GL, Garrido P, Nieva J, Steuer C, Overbeck TR, Bowles DW, Fox E, Riehl T, Chow-Maneval E, Simmons B, Cui N, Johnson A, Eng S, Wilson TR, Demetri GD, trial investigators| | PubMed
Interpretation of ceritinib clinical trial results and future combination therapy strategies for ALK-rearranged NSCLC.
Current Status and Future Perspectives on Neoadjuvant Therapy in Lung Cancer.
Blumenthal GM, Bunn PA, Chaft JE, McCoach CE, Perez EA, Scagliotti GV, Carbone DP, Aerts HJWL, Aisner DL, Bergh J, Berry DA, Jarkowski A, Botwood N, Cross DAE, Diehn M, Drezner NL, Doebele RC, Blakely CM, Eberhardt WEE, Felip E, Gianni L, Keller SP, Leavey PJ, Malik S, Pignatti F, Prowell TM, Redman MW, Rizvi NA, Rosell R, Rusch V, de Ruysscher D, Schwartz LH, Sridhara R, Stahel RA, Swisher S, Taube JM, Travis WD, Keegan P, Wiens JR, Wistuba II, Wynes MW, Hirsch FR, Kris MG| | PubMed
RAS nucleotide cycling underlies the SHP2 phosphatase dependence of mutant BRAF-, NF1- and RAS-driven cancers.
Nichols RJ, Haderk F, Stahlhut C, Schulze CJ, Hemmati G, Wildes D, Tzitzilonis C, Mordec K, Marquez A, Romero J, Hsieh T, Zaman A, Olivas V, McCoach C, Blakely CM, Wang Z, Kiss G, Koltun ES, Gill AL, Singh M, Goldsmith MA, Smith JAM, Bivona TG| | PubMed
Clinical Utility of Cell-Free DNA for the Detection of ALK Fusions and Genomic Mechanisms of ALK Inhibitor Resistance in Non-Small Cell Lung Cancer.
McCoach CE, Blakely CM, Banks KC, Levy B, Chue BM, Raymond VM, Le AT, Lee CE, Diaz J, Waqar SN, Purcell WT, Aisner DL, Davies KD, Lanman RB, Shaw AT, Doebele RC| | PubMed
Imaging PD-L1 Expression with ImmunoPET.
Truillet C, Oh HLJ, Yeo SP, Lee CY, Huynh LT, Wei J, Parker MFL, Blakely C, Sevillano N, Wang YH, Shen YS, Olivas V, Jami KM, Moroz A, Jego B, Jaumain E, Fong L, Craik CS, Chang AJ, Bivona TG, Wang CI, Evans MJ| | PubMed
Evolution and clinical impact of co-occurring genetic alterations in advanced-stage EGFR-mutant lung cancers.
Blakely CM, Watkins TBK, Wu W, Gini B, Chabon JJ, McCoach CE, McGranahan N, Wilson GA, Birkbak NJ, Olivas VR, Rotow J, Maynard A, Wang V, Gubens MA, Banks KC, Lanman RB, Caulin AF, St John J, Cordero AR, Giannikopoulos P, Simmons AD, Mack PC, Gandara DR, Husain H, Doebele RC, Riess JW, Diehn M, Swanton C, Bivona TG| | PubMed
Adjuvant Chemotherapy Guided by Molecular Profiling and Improved Outcomes in Early Stage, Non-Small-Cell Lung Cancer.
Woodard GA, Wang SX, Kratz JR, Zoon-Besselink CT, Chiang CY, Gubens MA, Jahan TM, Blakely CM, Jones KD, Mann MJ, Jablons DM| | PubMed
Novel computational method for predicting polytherapy switching strategies to overcome tumor heterogeneity and evolution.
Jonsson VD, Blakely CM, Lin L, Asthana S, Matni N, Olivas V, Pazarentzos E, Gubens MA, Bastian BC, Taylor BS, Doyle JC, Bivona TG| | PubMed
Inactivation of Capicua drives cancer metastasis.
Okimoto RA, Breitenbuecher F, Olivas VR, Wu W, Gini B, Hofree M, Asthana S, Hrustanovic G, Flanagan J, Tulpule A, Blakely CM, Haringsma HJ, Simmons AD, Gowen K, Suh J, Miller VA, Ali S, Schuler M, Bivona TG| | PubMed
Neoadjuvant Oncogene-Targeted Therapy in Early Stage Non-Small-Cell Lung Cancer as a Strategy to Improve Clinical Outcome and Identify Early Mechanisms of Resistance.
McCoach CE, Bivona TG, Blakely CM, Doebele RC| | PubMed
RAS-MAPK dependence underlies a rational polytherapy strategy in EML4-ALK-positive lung cancer.
Hrustanovic G, Olivas V, Pazarentzos E, Tulpule A, Asthana S, Blakely CM, Okimoto RA, Lin L, Neel DS, Sabnis A, Flanagan J, Chan E, Varella-Garcia M, Aisner DL, Vaishnavi A, Ou SH, Collisson EA, Ichihara E, Mack PC, Lovly CM, Karachaliou N, Rosell R, Riess JW, Doebele RC, Bivona TG| | PubMed
NF-κB-activating complex engaged in response to EGFR oncogene inhibition drives tumor cell survival and residual disease in lung cancer.
Blakely CM, Pazarentzos E, Olivas V, Asthana S, Yan JJ, Tan I, Hrustanovic G, Chan E, Lin L, Neel DS, Newton W, Bobb KL, Fouts TR, Meshulam J, Gubens MA, Jablons DM, Johnson JR, Bandyopadhyay S, Krogan NJ, Bivona TG| | PubMed
Resiliency of lung cancers to EGFR inhibitor treatment unveiled, offering opportunities to divide and conquer EGFR inhibitor resistance.
Hormone-induced protection against mammary tumorigenesis is conserved in multiple rat strains and identifies a core gene expression signature induced by pregnancy.
Blakely CM, Stoddard AJ, Belka GK, Dugan KD, Notarfrancesco KL, Moody SE, D'Cruz CM, Chodosh LA| | PubMed
Developmental stage determines the effects of MYC in the mammary epithelium.
Blakely CM, Sintasath L, D'Cruz CM, Hahn KT, Dugan KD, Belka GK, Chodosh LA| | PubMed
P52rIPK regulates the molecular cochaperone P58IPK to mediate control of the RNA-dependent protein kinase in response to cytoplasmic stress.
Gale M, Blakely CM, Darveau A, Romano PR, Korth MJ, Katze MG| | PubMed
The direct binding of the catalytic subunit of protein phosphatase 1 to the PKR protein kinase is necessary but not sufficient for inactivation and disruption of enzyme dimer formation.
Tan SL, Tareen SU, Melville MW, Blakely CM, Katze MG| | PubMed
Ser(2194) is a highly conserved major phosphorylation site of the hepatitis C virus nonstructural protein NS5A.
Katze MG, Kwieciszewski B, Goodlett DR, Blakely CM, Neddermann P, Tan SL, Aebersold R| | PubMed
Tissue specific expression of PKR protein kinase in aging B6D2F1 mice.