Dissecting Tumor Intrinsic and Immune Drivers of Resistance to Therapy in Non-Small Cell Lung Cancer


Damon Runyon - Mark Foundation Physician-Scientist (2020-Present)

Natalie Vokes, MD, The University of Texas MD Anderson Cancer Center

Natalie Vokes, MD

The treatment of non-small cell lung cancer (NSCLC) has changed dramatically with the development of immune-activating checkpoint inhibitors, given alone or with chemotherapy. However, most patients’ tumors eventually develop resistance to these drugs. Dr. Vokes is investigating this process by collecting data on the genetic and immune features of pre- and post-treatment tumors. She will then use computational algorithms to integrate these features into a model that predicts which patients are likely to respond to checkpoint inhibitor therapy and also sheds light on the difference between therapy given alone or with chemotherapy. A better understanding of how tumors evolve resistance will guide the design of more effective therapies for all patients and improve therapy selection for individuals.

Content courtesy of Damon Runyon Cancer Research Foundation

PUBLISHED RESEARCH

Reardon B, Moore ND, Moore NS, Kofman E, AlDubayan SH, Cheung ATM, Conway J, Elmarakeby H, Imamovic A, Kamran SC, Keenan T, Keliher D, Konieczkowski DJ, Liu D, Mouw KW, Park J, Vokes NI , Dietlein F, Van Allen EM. Integrating molecular profiles into clinical frameworks through the Molecular Oncology Almanac to prospectively guide precision oncology. Nat. Cancer. 2021.

Bakouny Z, Sadagopan A, Ravi P, Metaferia NY, Li J, AbuHammad S, Tang S, Denize T, Garner ER, Gao X, Braun DA, Hirsch L, Steinharter JA, Bouchard G, Walton E, West D, Labaki C, Dudani S, Gan CL, Sethunath V, Carvalho FLF, Imamovic A, Ricker C, Vokes NI, Nyman J, Berchuck JE, Park J, Hirsch MS, Haq R, Lee GSM, McGregor BA, Chang SL, Feldman AS, Wu CJ, McDermott DF, Heng DYC, Signoretti S, Van Allen EM, Choueiri TK, Viswanathan SR. Integrative clinical and molecular characterization of translocation renal cell carcinoma. Cell Reports. 2022.

Vokes NI, Chambers E, Nguyen T, Coolidge A, Lydon CA, Le X, Sholl L, Heymach JV, Nishino M, Van Allen EM, Jänne PA. Concurrent TP53 mutations facilitate resistance evolution in EGFR mutant lung adenocarcinoma. J Thorac Oncol. 2022.

Hong L, Aminu M, Li S, Lu X, Petranovic M, Saad MB, Chen P, Qin K, Varghese S, Rinsurongkawong W, Rinsurongkawong V, Spelman A, Elamin YY, Negrao MV, Skoulidis F, Gay CM, Cascone T, Gandhi SJ, Lin SH, Lee PP, Carter BW, Wu CC, Antonoff MB, Sepesi B, Lewis J, Gibbons DL, Vaporciyan AA, Le X, Jack Lee J, Roy-Chowdhuri S, Routbort MJ, Gainor JF, Heymach JV, Lou Y, Wu J, Zhang J, Vokes NI. Efficacy and clinicogenomic correlates of response to immune checkpoint inhibitors alone or with chemotherapy in non-small cell lung cancer. Nat Commun. 2023.

Vokes NI, Pan K, Le X. Efficacy of immunotherapy in oncogene-driven non-small-cell lung cancer. Ther Adv Med Oncol. 2023.

Boiarsky D, Lydon CA, Chambers ES, Sholl LM, Nishino M, Skoulidis F, Heymach JV, Luo J, Awad MA, Janne PA, Van Allen EM, Barbie DA, Vokes NI. Molecular markers of metastatic disease in KRAS mutant lung adenocarcinoma. Ann Oncol. 2023.

Saad MB, Hong L, Aminu M, Vokes NI, Chen P, Salehjahromi M, Qin K, Sujit SJ, Lu X, Young E, Al-Tashi Q, Qureshi R, Wu CC, Carter BW, Lin SH, Lee PP, Gandhi S, Chang JY, Li R, Gensheimer MF, Wakelee HA, Neal JW, Lee HS, Cheng C, Velcheti V, Lou Y, Petranovic M, Rinsurongkawong W, Le X, Rinsurongkawong V, Spelman A, Elamin YY, Negrao MV, Skoulidis F, Gay CM, Cascone T, Antonoff MB, Sepesi B, Lewis J, Wistuba II, Hazle JD, Chung C, Jaffray D, Gibbons DL, Vaporciyan A, Lee JJ, Heymach JV, Zhang J, Wu J. Predicting benefit from immune checkpoint inhibitors in patients with non-small-cell lung cancer by CT-based ensemble deep learning: a retrospective study. Lancet Digit Health. 2023.

Thummalapalli R, Ricciuti B, Bandlamudi C, Muldoon D, Rizvi H, Elkrief A, Luo J, Alessi JV, Pecci F, Lamberti G, Di Federico A, Hong L, Zhang J, Heymach JV, Gibbons DL, Plodkowski AJ, Ravichandran V, Donoghue MTA, Vanderbilt C, Ladanyi M, Rudin CM, Kris MG, Riely GJ, Chaft JE, Hellmann MD, Vokes NI, Awad MM, Schoenfeld AJ. Clinical and molecular features of long-term response to immune checkpoint inhibitors in patients with advanced non-small cell lung cancer. Clin Cancer Res. 2023.

Wang K, Du R, Roy-Chowdhuri S, Li ZT, Hong L, Vokes N, Elamin YY, Hume CB, Skoulidis F, Gay CM, Blumenschein G, Fossella FV, Tsao A, Zhang J, Karachaliou N, O’Brate A, Gann CN, Lewis J, Rinsurongkawong W, Lee JJ, Gibbons DL, Vaporciyan AA, Heymach JV, Altan M, Le X. Brief Report: Clinical Response, Toxicity, and Resistance Mechanisms to Osimertinib Plus MET Inhibitors in Patients With EGFR-Mutant MET-Amplified NSCLC. JTO Clin Res Rep. 2023.

Vokes NI, Galan Cobo A, Fernandez-Chas M, Molkentine D, Treviño S, Druker V, Qian Y, Patel S, Schmidt S, Hong L, Lewis J, Rinsurongkawong W, Rinsurongkawong V, Lee JJ, Negrao MV, Gibbons DL, Vaporciyan A, Le X, Wu J, Zhang J, Rigney U, Iyer S, Dean E, Heymach JV. ATM mutations associate with distinct co-mutational patterns and therapeutic vulnerabilities in NSCLC. Clin Cancer Res. 2023.

Seth S, Chen R, Liu Y, Fujimoto J, Hong L, Reuben A, Varghese S, Behrens C, McDowell T, Soto LS, Haymaker C, Weissferdt A, Kalhor N, Wu J, Le X, Vokes NI, Cheng C, Heymach JV, Gibbons DL, Futreal PA, Wistuba II, Kadara H, Zhang J, Moran C, Zhang J. Integrative genomic and transcriptomic profiling of pulmonary sarcomatoid carcinoma identifies molecular subtypes associated with distinct immune features and clinical outcomes. Cancer Innov. 2024.

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