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Start Over Author "Truini, A." Publisher american association for cancer research (aacr)
115 results on '"Truini, A."'

1. Supplementary Figure 1 from Combined Low Densities of FoxP3+ and CD3+ Tumor-Infiltrating Lymphocytes Identify Stage II Colorectal Cancer at High Risk of Progression

Author

Cavalleri, Tommaso, primary, Bianchi, Paolo, primary, Basso, Gianluca, primary, Celesti, Giuseppe, primary, Grizzi, Fabio, primary, Bossi, Paola, primary, Greco, Luana, primary, Pitrone, Calogero, primary, Valtorta, Emanuele, primary, Mauri, Gianluca, primary, Truini, Mauro, primary, Dall'Olio, Filippo Gustavo, primary, Brandi, Giovanni, primary, Sartore-Bianchi, Andrea, primary, Ricciardiello, Luigi, primary, Torri, Valter, primary, Rimassa, Lorenza, primary, Siena, Salvatore, primary, Mantovani, Alberto, primary, Malesci, Alberto, primary, and Laghi, Luigi, primary

Published
2023
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2. Supplementary Table 1 from Combined Low Densities of FoxP3+ and CD3+ Tumor-Infiltrating Lymphocytes Identify Stage II Colorectal Cancer at High Risk of Progression

Author

Cavalleri, Tommaso, primary, Bianchi, Paolo, primary, Basso, Gianluca, primary, Celesti, Giuseppe, primary, Grizzi, Fabio, primary, Bossi, Paola, primary, Greco, Luana, primary, Pitrone, Calogero, primary, Valtorta, Emanuele, primary, Mauri, Gianluca, primary, Truini, Mauro, primary, Dall'Olio, Filippo Gustavo, primary, Brandi, Giovanni, primary, Sartore-Bianchi, Andrea, primary, Ricciardiello, Luigi, primary, Torri, Valter, primary, Rimassa, Lorenza, primary, Siena, Salvatore, primary, Mantovani, Alberto, primary, Malesci, Alberto, primary, and Laghi, Luigi, primary

Published
2023
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3. Supplementary Table 4 from Combined Low Densities of FoxP3+ and CD3+ Tumor-Infiltrating Lymphocytes Identify Stage II Colorectal Cancer at High Risk of Progression

Author

Cavalleri, Tommaso, primary, Bianchi, Paolo, primary, Basso, Gianluca, primary, Celesti, Giuseppe, primary, Grizzi, Fabio, primary, Bossi, Paola, primary, Greco, Luana, primary, Pitrone, Calogero, primary, Valtorta, Emanuele, primary, Mauri, Gianluca, primary, Truini, Mauro, primary, Dall'Olio, Filippo Gustavo, primary, Brandi, Giovanni, primary, Sartore-Bianchi, Andrea, primary, Ricciardiello, Luigi, primary, Torri, Valter, primary, Rimassa, Lorenza, primary, Siena, Salvatore, primary, Mantovani, Alberto, primary, Malesci, Alberto, primary, and Laghi, Luigi, primary

Published
2023
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4. Data from Combined Low Densities of FoxP3+ and CD3+ Tumor-Infiltrating Lymphocytes Identify Stage II Colorectal Cancer at High Risk of Progression

Author

Cavalleri, Tommaso, primary, Bianchi, Paolo, primary, Basso, Gianluca, primary, Celesti, Giuseppe, primary, Grizzi, Fabio, primary, Bossi, Paola, primary, Greco, Luana, primary, Pitrone, Calogero, primary, Valtorta, Emanuele, primary, Mauri, Gianluca, primary, Truini, Mauro, primary, Dall'Olio, Filippo Gustavo, primary, Brandi, Giovanni, primary, Sartore-Bianchi, Andrea, primary, Ricciardiello, Luigi, primary, Torri, Valter, primary, Rimassa, Lorenza, primary, Siena, Salvatore, primary, Mantovani, Alberto, primary, Malesci, Alberto, primary, and Laghi, Luigi, primary

Published
2023
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5. Supplementary Table 2 from Combined Low Densities of FoxP3+ and CD3+ Tumor-Infiltrating Lymphocytes Identify Stage II Colorectal Cancer at High Risk of Progression

Author

Cavalleri, Tommaso, primary, Bianchi, Paolo, primary, Basso, Gianluca, primary, Celesti, Giuseppe, primary, Grizzi, Fabio, primary, Bossi, Paola, primary, Greco, Luana, primary, Pitrone, Calogero, primary, Valtorta, Emanuele, primary, Mauri, Gianluca, primary, Truini, Mauro, primary, Dall'Olio, Filippo Gustavo, primary, Brandi, Giovanni, primary, Sartore-Bianchi, Andrea, primary, Ricciardiello, Luigi, primary, Torri, Valter, primary, Rimassa, Lorenza, primary, Siena, Salvatore, primary, Mantovani, Alberto, primary, Malesci, Alberto, primary, and Laghi, Luigi, primary

Published
2023
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6. Supplementary Table 3 from Combined Low Densities of FoxP3+ and CD3+ Tumor-Infiltrating Lymphocytes Identify Stage II Colorectal Cancer at High Risk of Progression

Author

Cavalleri, Tommaso, primary, Bianchi, Paolo, primary, Basso, Gianluca, primary, Celesti, Giuseppe, primary, Grizzi, Fabio, primary, Bossi, Paola, primary, Greco, Luana, primary, Pitrone, Calogero, primary, Valtorta, Emanuele, primary, Mauri, Gianluca, primary, Truini, Mauro, primary, Dall'Olio, Filippo Gustavo, primary, Brandi, Giovanni, primary, Sartore-Bianchi, Andrea, primary, Ricciardiello, Luigi, primary, Torri, Valter, primary, Rimassa, Lorenza, primary, Siena, Salvatore, primary, Mantovani, Alberto, primary, Malesci, Alberto, primary, and Laghi, Luigi, primary

Published
2023
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7. Supplementary Figure 2 from Combined Low Densities of FoxP3+ and CD3+ Tumor-Infiltrating Lymphocytes Identify Stage II Colorectal Cancer at High Risk of Progression

Author

Cavalleri, Tommaso, primary, Bianchi, Paolo, primary, Basso, Gianluca, primary, Celesti, Giuseppe, primary, Grizzi, Fabio, primary, Bossi, Paola, primary, Greco, Luana, primary, Pitrone, Calogero, primary, Valtorta, Emanuele, primary, Mauri, Gianluca, primary, Truini, Mauro, primary, Dall'Olio, Filippo Gustavo, primary, Brandi, Giovanni, primary, Sartore-Bianchi, Andrea, primary, Ricciardiello, Luigi, primary, Torri, Valter, primary, Rimassa, Lorenza, primary, Siena, Salvatore, primary, Mantovani, Alberto, primary, Malesci, Alberto, primary, and Laghi, Luigi, primary

Published
2023
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8. Data from Role of CXCL13-CXCR5 Crosstalk Between Malignant Neuroblastoma Cells and Schwannian Stromal Cells in Neuroblastic Tumors

Author

Del Grosso, Federica, primary, Coco, Simona, primary, Scaruffi, Paola, primary, Stigliani, Sara, primary, Valdora, Francesca, primary, Benelli, Roberto, primary, Salvi, Sandra, primary, Boccardo, Simona, primary, Truini, Mauro, primary, Croce, Michela, primary, Ferrini, Silvano, primary, Longo, Luca, primary, and Tonini, Gian Paolo, primary

Published
2023
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9. Table S1 from Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer

Author

Gettinger, Scott, primary, Choi, Jungmin, primary, Hastings, Katherine, primary, Truini, Anna, primary, Datar, Ila, primary, Sowell, Ryan, primary, Wurtz, Anna, primary, Dong, Weilai, primary, Cai, Guoping, primary, Melnick, Mary Ann, primary, Du, Victor Y., primary, Schlessinger, Joseph, primary, Goldberg, Sarah B., primary, Chiang, Anne, primary, Sanmamed, Miguel F., primary, Melero, Ignacio, primary, Agorreta, Jackeline, primary, Montuenga, Luis M., primary, Lifton, Richard, primary, Ferrone, Soldano, primary, Kavathas, Paula, primary, Rimm, David L., primary, Kaech, Susan M., primary, Schalper, Kurt, primary, Herbst, Roy S., primary, and Politi, Katerina, primary

Published
2023
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10. Supplementary Figure Legends from Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer

Author

Gettinger, Scott, primary, Choi, Jungmin, primary, Hastings, Katherine, primary, Truini, Anna, primary, Datar, Ila, primary, Sowell, Ryan, primary, Wurtz, Anna, primary, Dong, Weilai, primary, Cai, Guoping, primary, Melnick, Mary Ann, primary, Du, Victor Y., primary, Schlessinger, Joseph, primary, Goldberg, Sarah B., primary, Chiang, Anne, primary, Sanmamed, Miguel F., primary, Melero, Ignacio, primary, Agorreta, Jackeline, primary, Montuenga, Luis M., primary, Lifton, Richard, primary, Ferrone, Soldano, primary, Kavathas, Paula, primary, Rimm, David L., primary, Kaech, Susan M., primary, Schalper, Kurt, primary, Herbst, Roy S., primary, and Politi, Katerina, primary

Published
2023
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11. Data from Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer

Author

Gettinger, Scott, primary, Choi, Jungmin, primary, Hastings, Katherine, primary, Truini, Anna, primary, Datar, Ila, primary, Sowell, Ryan, primary, Wurtz, Anna, primary, Dong, Weilai, primary, Cai, Guoping, primary, Melnick, Mary Ann, primary, Du, Victor Y., primary, Schlessinger, Joseph, primary, Goldberg, Sarah B., primary, Chiang, Anne, primary, Sanmamed, Miguel F., primary, Melero, Ignacio, primary, Agorreta, Jackeline, primary, Montuenga, Luis M., primary, Lifton, Richard, primary, Ferrone, Soldano, primary, Kavathas, Paula, primary, Rimm, David L., primary, Kaech, Susan M., primary, Schalper, Kurt, primary, Herbst, Roy S., primary, and Politi, Katerina, primary

Published
2023
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12. Supplementary Table 2 from Role of CXCL13-CXCR5 Crosstalk Between Malignant Neuroblastoma Cells and Schwannian Stromal Cells in Neuroblastic Tumors

Author

Del Grosso, Federica, primary, Coco, Simona, primary, Scaruffi, Paola, primary, Stigliani, Sara, primary, Valdora, Francesca, primary, Benelli, Roberto, primary, Salvi, Sandra, primary, Boccardo, Simona, primary, Truini, Mauro, primary, Croce, Michela, primary, Ferrini, Silvano, primary, Longo, Luca, primary, and Tonini, Gian Paolo, primary

Published
2023
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13. Data from Tumor Heterogeneity and Lesion-Specific Response to Targeted Therapy in Colorectal Cancer

Author

Russo, Mariangela, primary, Siravegna, Giulia, primary, Blaszkowsky, Lawrence S., primary, Corti, Giorgio, primary, Crisafulli, Giovanni, primary, Ahronian, Leanne G., primary, Mussolin, Benedetta, primary, Kwak, Eunice L., primary, Buscarino, Michela, primary, Lazzari, Luca, primary, Valtorta, Emanuele, primary, Truini, Mauro, primary, Jessop, Nicholas A., primary, Robinson, Hayley E., primary, Hong, Theodore S., primary, Mino-Kenudson, Mari, primary, Di Nicolantonio, Federica, primary, Thabet, Ashraf, primary, Sartore-Bianchi, Andrea, primary, Siena, Salvatore, primary, Iafrate, A. John, primary, Bardelli, Alberto, primary, and Corcoran, Ryan B., primary

Published
2023
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14. Supplementary Figures S1 - S3, Tables S1 - S6 from Tumor Heterogeneity and Lesion-Specific Response to Targeted Therapy in Colorectal Cancer

Author

Russo, Mariangela, primary, Siravegna, Giulia, primary, Blaszkowsky, Lawrence S., primary, Corti, Giorgio, primary, Crisafulli, Giovanni, primary, Ahronian, Leanne G., primary, Mussolin, Benedetta, primary, Kwak, Eunice L., primary, Buscarino, Michela, primary, Lazzari, Luca, primary, Valtorta, Emanuele, primary, Truini, Mauro, primary, Jessop, Nicholas A., primary, Robinson, Hayley E., primary, Hong, Theodore S., primary, Mino-Kenudson, Mari, primary, Di Nicolantonio, Federica, primary, Thabet, Ashraf, primary, Sartore-Bianchi, Andrea, primary, Siena, Salvatore, primary, Iafrate, A. John, primary, Bardelli, Alberto, primary, and Corcoran, Ryan B., primary

Published
2023
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15. Supplementary Figures from Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer

Author

Gettinger, Scott, primary, Choi, Jungmin, primary, Hastings, Katherine, primary, Truini, Anna, primary, Datar, Ila, primary, Sowell, Ryan, primary, Wurtz, Anna, primary, Dong, Weilai, primary, Cai, Guoping, primary, Melnick, Mary Ann, primary, Du, Victor Y., primary, Schlessinger, Joseph, primary, Goldberg, Sarah B., primary, Chiang, Anne, primary, Sanmamed, Miguel F., primary, Melero, Ignacio, primary, Agorreta, Jackeline, primary, Montuenga, Luis M., primary, Lifton, Richard, primary, Ferrone, Soldano, primary, Kavathas, Paula, primary, Rimm, David L., primary, Kaech, Susan M., primary, Schalper, Kurt, primary, Herbst, Roy S., primary, and Politi, Katerina, primary

Published
2023
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16. Supplementary Table 1 from Role of CXCL13-CXCR5 Crosstalk Between Malignant Neuroblastoma Cells and Schwannian Stromal Cells in Neuroblastic Tumors

Author

Del Grosso, Federica, primary, Coco, Simona, primary, Scaruffi, Paola, primary, Stigliani, Sara, primary, Valdora, Francesca, primary, Benelli, Roberto, primary, Salvi, Sandra, primary, Boccardo, Simona, primary, Truini, Mauro, primary, Croce, Michela, primary, Ferrini, Silvano, primary, Longo, Luca, primary, and Tonini, Gian Paolo, primary

Published
2023
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17. Supplementary Methods from Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer

Author

Gettinger, Scott, primary, Choi, Jungmin, primary, Hastings, Katherine, primary, Truini, Anna, primary, Datar, Ila, primary, Sowell, Ryan, primary, Wurtz, Anna, primary, Dong, Weilai, primary, Cai, Guoping, primary, Melnick, Mary Ann, primary, Du, Victor Y., primary, Schlessinger, Joseph, primary, Goldberg, Sarah B., primary, Chiang, Anne, primary, Sanmamed, Miguel F., primary, Melero, Ignacio, primary, Agorreta, Jackeline, primary, Montuenga, Luis M., primary, Lifton, Richard, primary, Ferrone, Soldano, primary, Kavathas, Paula, primary, Rimm, David L., primary, Kaech, Susan M., primary, Schalper, Kurt, primary, Herbst, Roy S., primary, and Politi, Katerina, primary

Published
2023
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18. Supplementary Figure 2 from Combined Low Densities of FoxP3+ and CD3+ Tumor-Infiltrating Lymphocytes Identify Stage II Colorectal Cancer at High Risk of Progression

Author

Luigi Laghi, Alberto Malesci, Alberto Mantovani, Salvatore Siena, Lorenza Rimassa, Valter Torri, Luigi Ricciardiello, Andrea Sartore-Bianchi, Giovanni Brandi, Filippo Gustavo Dall'Olio, Mauro Truini, Gianluca Mauri, Emanuele Valtorta, Calogero Pitrone, Luana Greco, Paola Bossi, Fabio Grizzi, Giuseppe Celesti, Gianluca Basso, Paolo Bianchi, and Tommaso Cavalleri

Abstract

Kaplan-Meier curves for the duration of disease-free survival in joined cohorts with stage II CRC as to adjuvant treatment.

Published
2023
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19. Supplementary Table 4 from Combined Low Densities of FoxP3+ and CD3+ Tumor-Infiltrating Lymphocytes Identify Stage II Colorectal Cancer at High Risk of Progression

Author

Luigi Laghi, Alberto Malesci, Alberto Mantovani, Salvatore Siena, Lorenza Rimassa, Valter Torri, Luigi Ricciardiello, Andrea Sartore-Bianchi, Giovanni Brandi, Filippo Gustavo Dall'Olio, Mauro Truini, Gianluca Mauri, Emanuele Valtorta, Calogero Pitrone, Luana Greco, Paola Bossi, Fabio Grizzi, Giuseppe Celesti, Gianluca Basso, Paolo Bianchi, and Tommaso Cavalleri

Abstract

Low densities of FoxP3+ and CD3+ TILs, and their combination, to predict disease-free survival (DFS) in stage II MSS CRC Validation set.

Published
2023
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20. Data from Combined Low Densities of FoxP3+ and CD3+ Tumor-Infiltrating Lymphocytes Identify Stage II Colorectal Cancer at High Risk of Progression

Author

Luigi Laghi, Alberto Malesci, Alberto Mantovani, Salvatore Siena, Lorenza Rimassa, Valter Torri, Luigi Ricciardiello, Andrea Sartore-Bianchi, Giovanni Brandi, Filippo Gustavo Dall'Olio, Mauro Truini, Gianluca Mauri, Emanuele Valtorta, Calogero Pitrone, Luana Greco, Paola Bossi, Fabio Grizzi, Giuseppe Celesti, Gianluca Basso, Paolo Bianchi, and Tommaso Cavalleri

Abstract

The densities of CD3+ and CD8+ tumor-infiltrating lymphocytes (TILs), combined with tumor–node–metastasis (TNM) staging, have prognostic value for patients with nonmetastatic colorectal cancer. We compared the prognostic value of CD3+ and FoxP3+ TILs at the invasive front, TNM classifiers, and microsatellite (MS) status in a trial set of patients with stage II and III colorectal cancer (n = 413), by recursive partitioning with a classification and regression tree (CART). Significant prognostic factors and interactions were reassessed by logistic regression and Cox proportional-hazards modeling in the trial and a validation set (n = 215) of patients with stage II colorectal cancer. In the trial set, CART indicated that TIL numbers were of value only in predicting recurrence risk for stage II cancers, where low densities of FoxP3+ TILs ranked first and low densities of CD3+ TILs further stratifying risk. Multivariate analysis showed that TILs interacted with tumor stage (FoxP3+, P = 0.06; CD3+, P = 0.02) and MS instability (MSI; FoxP3+; P = 0.02). In stage II MS-stable cancers, concomitant low densities of both FoxP3+ and CD3+ TILs identified patients with the highest progression risk in the trial [HR 7.24; 95% confidence interval (CI), 3.41–15.4; P < 0.001] and the validation (HR 15.16; 95% CI, 3.43–66.9; P < 0.001) sets. FoxP3+ and CD3+ TIL load in colorectal cancer was more informative than other prognostic factors before the cancer progressed to lymph nodes. This prognostic information about TILs, including FoxP3+ cells, suggests that randomized controlled trials might be refined to include interactions between TNM status, molecular classifiers, and postsurgical treatments.

Published
2023
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21. Supplementary Table 3 from Combined Low Densities of FoxP3+ and CD3+ Tumor-Infiltrating Lymphocytes Identify Stage II Colorectal Cancer at High Risk of Progression

Author

Luigi Laghi, Alberto Malesci, Alberto Mantovani, Salvatore Siena, Lorenza Rimassa, Valter Torri, Luigi Ricciardiello, Andrea Sartore-Bianchi, Giovanni Brandi, Filippo Gustavo Dall'Olio, Mauro Truini, Gianluca Mauri, Emanuele Valtorta, Calogero Pitrone, Luana Greco, Paola Bossi, Fabio Grizzi, Giuseppe Celesti, Gianluca Basso, Paolo Bianchi, and Tommaso Cavalleri

Abstract

Densities of FoxP3+ and CD3+ TILs in validation set (161 stage II CRC), by clinical-pathological variables.

Published
2023
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22. Supplementary Table 1 from Combined Low Densities of FoxP3+ and CD3+ Tumor-Infiltrating Lymphocytes Identify Stage II Colorectal Cancer at High Risk of Progression

Author

Luigi Laghi, Alberto Malesci, Alberto Mantovani, Salvatore Siena, Lorenza Rimassa, Valter Torri, Luigi Ricciardiello, Andrea Sartore-Bianchi, Giovanni Brandi, Filippo Gustavo Dall'Olio, Mauro Truini, Gianluca Mauri, Emanuele Valtorta, Calogero Pitrone, Luana Greco, Paola Bossi, Fabio Grizzi, Giuseppe Celesti, Gianluca Basso, Paolo Bianchi, and Tommaso Cavalleri

Abstract

Densities of FoxP3+ and CD3+ TILs in 413 stage II-III CRC, by clinical-pathological variables.

Published
2023
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23. Supplementary Figure 1 from Combined Low Densities of FoxP3+ and CD3+ Tumor-Infiltrating Lymphocytes Identify Stage II Colorectal Cancer at High Risk of Progression

Author

Luigi Laghi, Alberto Malesci, Alberto Mantovani, Salvatore Siena, Lorenza Rimassa, Valter Torri, Luigi Ricciardiello, Andrea Sartore-Bianchi, Giovanni Brandi, Filippo Gustavo Dall'Olio, Mauro Truini, Gianluca Mauri, Emanuele Valtorta, Calogero Pitrone, Luana Greco, Paola Bossi, Fabio Grizzi, Giuseppe Celesti, Gianluca Basso, Paolo Bianchi, and Tommaso Cavalleri

Abstract

ROC curves for densities of FoxP3+ and CD3+ TILs as predictors of postsurgical recurrence in patients with stage II MSS CRC, validation set.

Published
2023
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24. Supplementary Table 2 from Combined Low Densities of FoxP3+ and CD3+ Tumor-Infiltrating Lymphocytes Identify Stage II Colorectal Cancer at High Risk of Progression

Author

Luigi Laghi, Alberto Malesci, Alberto Mantovani, Salvatore Siena, Lorenza Rimassa, Valter Torri, Luigi Ricciardiello, Andrea Sartore-Bianchi, Giovanni Brandi, Filippo Gustavo Dall'Olio, Mauro Truini, Gianluca Mauri, Emanuele Valtorta, Calogero Pitrone, Luana Greco, Paola Bossi, Fabio Grizzi, Giuseppe Celesti, Gianluca Basso, Paolo Bianchi, and Tommaso Cavalleri

Abstract

Predictors of post-surgical recurrence in 413 CRC patients with stage II/III CRC.

Published
2023
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25. Supplementary Table 1 from Role of CXCL13-CXCR5 Crosstalk Between Malignant Neuroblastoma Cells and Schwannian Stromal Cells in Neuroblastic Tumors

Author

Gian Paolo Tonini, Luca Longo, Silvano Ferrini, Michela Croce, Mauro Truini, Simona Boccardo, Sandra Salvi, Roberto Benelli, Francesca Valdora, Sara Stigliani, Paola Scaruffi, Simona Coco, and Federica Del Grosso

Abstract

Supplementary Table 1 from Role of CXCL13-CXCR5 Crosstalk Between Malignant Neuroblastoma Cells and Schwannian Stromal Cells in Neuroblastic Tumors

Published
2023
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26. Table S1 from Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer

Author

Katerina Politi, Roy S. Herbst, Kurt Schalper, Susan M. Kaech, David L. Rimm, Paula Kavathas, Soldano Ferrone, Richard Lifton, Luis M. Montuenga, Jackeline Agorreta, Ignacio Melero, Miguel F. Sanmamed, Anne Chiang, Sarah B. Goldberg, Joseph Schlessinger, Victor Y. Du, Mary Ann Melnick, Guoping Cai, Weilai Dong, Anna Wurtz, Ryan Sowell, Ila Datar, Anna Truini, Katherine Hastings, Jungmin Choi, and Scott Gettinger

Abstract

Table with Details of Patient Characteristics

Published
2023
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27. Supplementary Methods from Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer

Author

Katerina Politi, Roy S. Herbst, Kurt Schalper, Susan M. Kaech, David L. Rimm, Paula Kavathas, Soldano Ferrone, Richard Lifton, Luis M. Montuenga, Jackeline Agorreta, Ignacio Melero, Miguel F. Sanmamed, Anne Chiang, Sarah B. Goldberg, Joseph Schlessinger, Victor Y. Du, Mary Ann Melnick, Guoping Cai, Weilai Dong, Anna Wurtz, Ryan Sowell, Ila Datar, Anna Truini, Katherine Hastings, Jungmin Choi, and Scott Gettinger

Abstract

Methods for quantitative immunofluorescence and IFN gamma treatment of PDXs

Published
2023
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28. Supplementary Table 2 from Role of CXCL13-CXCR5 Crosstalk Between Malignant Neuroblastoma Cells and Schwannian Stromal Cells in Neuroblastic Tumors

Author

Gian Paolo Tonini, Luca Longo, Silvano Ferrini, Michela Croce, Mauro Truini, Simona Boccardo, Sandra Salvi, Roberto Benelli, Francesca Valdora, Sara Stigliani, Paola Scaruffi, Simona Coco, and Federica Del Grosso

Abstract

Supplementary Table 2 from Role of CXCL13-CXCR5 Crosstalk Between Malignant Neuroblastoma Cells and Schwannian Stromal Cells in Neuroblastic Tumors

Published
2023
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29. Supplementary Figures S1 - S3, Tables S1 - S6 from Tumor Heterogeneity and Lesion-Specific Response to Targeted Therapy in Colorectal Cancer

Author

Ryan B. Corcoran, Alberto Bardelli, A. John Iafrate, Salvatore Siena, Andrea Sartore-Bianchi, Ashraf Thabet, Federica Di Nicolantonio, Mari Mino-Kenudson, Theodore S. Hong, Hayley E. Robinson, Nicholas A. Jessop, Mauro Truini, Emanuele Valtorta, Luca Lazzari, Michela Buscarino, Eunice L. Kwak, Benedetta Mussolin, Leanne G. Ahronian, Giovanni Crisafulli, Giorgio Corti, Lawrence S. Blaszkowsky, Giulia Siravegna, and Mariangela Russo

Abstract

Supplementary Figure S1. MEK1 K57 mutation confers resistance to anti-EGFR antibodies in CRC preclinical models. Supplementary Figure S2. Dual blockade of EGFR and MEK restores sensitivity to CRC cells expressing MEK1 K57N or K57T. Supplementary Figure S3. Longitudinal analysis of founder mutations in patient plasma during panitumumab and trametinib treatment. Supplementary Table S1. 1000 gene sequencing panel. Supplementary Table S2. 40 gene targeted sequencing panel. Supplementary Table S3. Summary of targeted sequencing and ddPCR data on tissue specimens. Supplementary Table S4. Next generation sequencing data from plasma ctDNA. Supplementary Table S5. Summary of serial ctDNA analyses. Supplementary Table S6. Ratio of resistance-associated genetic alterations and founder mutations in serial plasma ctDNA timepoints.

Published
2023
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30. Supplementary Figures from Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer

Author

Katerina Politi, Roy S. Herbst, Kurt Schalper, Susan M. Kaech, David L. Rimm, Paula Kavathas, Soldano Ferrone, Richard Lifton, Luis M. Montuenga, Jackeline Agorreta, Ignacio Melero, Miguel F. Sanmamed, Anne Chiang, Sarah B. Goldberg, Joseph Schlessinger, Victor Y. Du, Mary Ann Melnick, Guoping Cai, Weilai Dong, Anna Wurtz, Ryan Sowell, Ila Datar, Anna Truini, Katherine Hastings, Jungmin Choi, and Scott Gettinger

Abstract

Supplementary Figures S1-S8

Published
2023
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31. Supplementary Figure Legends from Molecular Landscape of Acquired Resistance to Targeted Therapy Combinations in BRAF-Mutant Colorectal Cancer

Author

Oddo, Daniele, primary, Sennott, Erin M., primary, Barault, Ludovic, primary, Valtorta, Emanuele, primary, Arena, Sabrina, primary, Cassingena, Andrea, primary, Filiciotto, Genny, primary, Marzolla, Giulia, primary, Elez, Elena, primary, van Geel, Robin M.J.M., primary, Bartolini, Alice, primary, Crisafulli, Giovanni, primary, Boscaro, Valentina, primary, Godfrey, Jason T., primary, Buscarino, Michela, primary, Cancelliere, Carlotta, primary, Linnebacher, Michael, primary, Corti, Giorgio, primary, Truini, Mauro, primary, Siravegna, Giulia, primary, Grasselli, Julieta, primary, Gallicchio, Margherita, primary, Bernards, René, primary, Schellens, Jan H.M., primary, Tabernero, Josep, primary, Engelman, Jeffrey A., primary, Sartore-Bianchi, Andrea, primary, Bardelli, Alberto, primary, Siena, Salvatore, primary, Corcoran, Ryan B., primary, and Di Nicolantonio, Federica, primary

Published
2023
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32. Supplementary Materials and Methods from Molecular Landscape of Acquired Resistance to Targeted Therapy Combinations in BRAF-Mutant Colorectal Cancer

Author

Oddo, Daniele, primary, Sennott, Erin M., primary, Barault, Ludovic, primary, Valtorta, Emanuele, primary, Arena, Sabrina, primary, Cassingena, Andrea, primary, Filiciotto, Genny, primary, Marzolla, Giulia, primary, Elez, Elena, primary, van Geel, Robin M.J.M., primary, Bartolini, Alice, primary, Crisafulli, Giovanni, primary, Boscaro, Valentina, primary, Godfrey, Jason T., primary, Buscarino, Michela, primary, Cancelliere, Carlotta, primary, Linnebacher, Michael, primary, Corti, Giorgio, primary, Truini, Mauro, primary, Siravegna, Giulia, primary, Grasselli, Julieta, primary, Gallicchio, Margherita, primary, Bernards, René, primary, Schellens, Jan H.M., primary, Tabernero, Josep, primary, Engelman, Jeffrey A., primary, Sartore-Bianchi, Andrea, primary, Bardelli, Alberto, primary, Siena, Salvatore, primary, Corcoran, Ryan B., primary, and Di Nicolantonio, Federica, primary

Published
2023
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33. Data from Molecular Landscape of Acquired Resistance to Targeted Therapy Combinations in BRAF-Mutant Colorectal Cancer

Author

Oddo, Daniele, primary, Sennott, Erin M., primary, Barault, Ludovic, primary, Valtorta, Emanuele, primary, Arena, Sabrina, primary, Cassingena, Andrea, primary, Filiciotto, Genny, primary, Marzolla, Giulia, primary, Elez, Elena, primary, van Geel, Robin M.J.M., primary, Bartolini, Alice, primary, Crisafulli, Giovanni, primary, Boscaro, Valentina, primary, Godfrey, Jason T., primary, Buscarino, Michela, primary, Cancelliere, Carlotta, primary, Linnebacher, Michael, primary, Corti, Giorgio, primary, Truini, Mauro, primary, Siravegna, Giulia, primary, Grasselli, Julieta, primary, Gallicchio, Margherita, primary, Bernards, René, primary, Schellens, Jan H.M., primary, Tabernero, Josep, primary, Engelman, Jeffrey A., primary, Sartore-Bianchi, Andrea, primary, Bardelli, Alberto, primary, Siena, Salvatore, primary, Corcoran, Ryan B., primary, and Di Nicolantonio, Federica, primary

Published
2023
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34. Supplementary Figures and Tables from Molecular Landscape of Acquired Resistance to Targeted Therapy Combinations in BRAF-Mutant Colorectal Cancer

Author

Oddo, Daniele, primary, Sennott, Erin M., primary, Barault, Ludovic, primary, Valtorta, Emanuele, primary, Arena, Sabrina, primary, Cassingena, Andrea, primary, Filiciotto, Genny, primary, Marzolla, Giulia, primary, Elez, Elena, primary, van Geel, Robin M.J.M., primary, Bartolini, Alice, primary, Crisafulli, Giovanni, primary, Boscaro, Valentina, primary, Godfrey, Jason T., primary, Buscarino, Michela, primary, Cancelliere, Carlotta, primary, Linnebacher, Michael, primary, Corti, Giorgio, primary, Truini, Mauro, primary, Siravegna, Giulia, primary, Grasselli, Julieta, primary, Gallicchio, Margherita, primary, Bernards, René, primary, Schellens, Jan H.M., primary, Tabernero, Josep, primary, Engelman, Jeffrey A., primary, Sartore-Bianchi, Andrea, primary, Bardelli, Alberto, primary, Siena, Salvatore, primary, Corcoran, Ryan B., primary, and Di Nicolantonio, Federica, primary

Published
2023
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35. Supplementary Figure S5 from Epigenetic Inactivation of microRNA-34b/c Predicts Poor Disease-Free Survival in Early-Stage Lung Adenocarcinoma

Author

Nadal, Ernest, primary, Chen, Guoan, primary, Gallegos, Marc, primary, Lin, Lin, primary, Ferrer-Torres, Daysha, primary, Truini, Anna, primary, Wang, Zhuwen, primary, Lin, Jules, primary, Reddy, Rishindra M., primary, Llatjos, Roger, primary, Escobar, Ignacio, primary, Moya, Juan, primary, Chang, Andrew C., primary, Cardenal, Felipe, primary, Capellà, Gabriel, primary, and Beer, David G., primary

Published
2023
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36. Supplementary Data from The EGFR Exon 19 Mutant L747-A750>P Exhibits Distinct Sensitivity to Tyrosine Kinase Inhibitors in Lung Adenocarcinoma

Author

Truini, Anna, primary, Starrett, Jacqueline H., primary, Stewart, Tyler, primary, Ashtekar, Kumar, primary, Walther, Zenta, primary, Wurtz, Anna, primary, Lu, David, primary, Park, Jin H., primary, DeVeaux, Michelle, primary, Song, Xiaoling, primary, Gettinger, Scott, primary, Zelterman, Daniel, primary, Lemmon, Mark A., primary, Goldberg, Sarah B., primary, and Politi, Katerina, primary

Published
2023
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37. Supplementary Tables S1-S6 from Epigenetic Inactivation of microRNA-34b/c Predicts Poor Disease-Free Survival in Early-Stage Lung Adenocarcinoma

Author

Nadal, Ernest, primary, Chen, Guoan, primary, Gallegos, Marc, primary, Lin, Lin, primary, Ferrer-Torres, Daysha, primary, Truini, Anna, primary, Wang, Zhuwen, primary, Lin, Jules, primary, Reddy, Rishindra M., primary, Llatjos, Roger, primary, Escobar, Ignacio, primary, Moya, Juan, primary, Chang, Andrew C., primary, Cardenal, Felipe, primary, Capellà, Gabriel, primary, and Beer, David G., primary

Published
2023
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38. Data from The EGFR Exon 19 Mutant L747-A750>P Exhibits Distinct Sensitivity to Tyrosine Kinase Inhibitors in Lung Adenocarcinoma

Author

Katerina Politi, Sarah B. Goldberg, Mark A. Lemmon, Daniel Zelterman, Scott Gettinger, Xiaoling Song, Michelle DeVeaux, Jin H. Park, David Lu, Anna Wurtz, Zenta Walther, Kumar Ashtekar, Tyler Stewart, Jacqueline H. Starrett, and Anna Truini

Abstract

Purpose:EGFR exon 19 deletion (Ex19Del) mutations account for approximately 60% of lung cancer–associated EGFR mutations and include a heterogeneous group of mutations. Although they are associated with benefit from tyrosine kinase inhibitors (TKI), the relative inhibitor sensitivity of individual Ex19Del mutations is unknown.Experimental Design: We studied the TKI sensitivity and structural features of common Ex19Del mutations and the consequences for patient outcomes on TKI treatment.Results:We found that the L747-A750>P mutation, which represents about 4% of all Ex19Del mutations, displays unique inhibitor selectivity. L747-A750>P differs from other Ex19Del mutations in not being suppressed completely by erlotinib or osimertinib, yet is completely inhibited by low doses of afatinib. The HCC4006 cell line (with the L747-A750>P mutation) exhibited increased sensitivity to afatinib over erlotinib and osimertinib, and computational modeling suggests explanations for this sensitivity pattern. Clinically, patients with EGFR L747-A750>P mutant tumors showed inferior outcomes when treated with erlotinib than patients with E746-A750 mutant tumors.Conclusions:These results highlight important differences between specific Ex19Del mutations that may be relevant for optimizing TKI choice for patients.

Published
2023
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39. Supplementary Figure S7 from Epigenetic Inactivation of microRNA-34b/c Predicts Poor Disease-Free Survival in Early-Stage Lung Adenocarcinoma

Author

David G. Beer, Gabriel Capellà, Felipe Cardenal, Andrew C. Chang, Juan Moya, Ignacio Escobar, Roger Llatjos, Rishindra M. Reddy, Jules Lin, Zhuwen Wang, Anna Truini, Daysha Ferrer-Torres, Lin Lin, Marc Gallegos, Guoan Chen, and Ernest Nadal

Abstract

PDF file 103K, Cisplatin chemosensitivity in SK-LU-1 miR-34b/c transfected cells

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2023
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40. Supplementary Tables S1-S6 from Epigenetic Inactivation of microRNA-34b/c Predicts Poor Disease-Free Survival in Early-Stage Lung Adenocarcinoma

Author

David G. Beer, Gabriel Capellà, Felipe Cardenal, Andrew C. Chang, Juan Moya, Ignacio Escobar, Roger Llatjos, Rishindra M. Reddy, Jules Lin, Zhuwen Wang, Anna Truini, Daysha Ferrer-Torres, Lin Lin, Marc Gallegos, Guoan Chen, and Ernest Nadal

Abstract

PDF file115K, Suppl.Table S1. Patient characteristics. Suppl.Table S2. Lung AC lines with TP53 mutation. Suppl.Table S3. Primers used for qRT-PCR. Suppl.Table S4. Correlation between tumors miR-34b/c expression and clinical and molecular variables. Suppl.Table S5. Multivariate Cox model for DFS based upon miR-34b/c methylation (continuous). Suppl.Table S6. Multivariate Cox model for OS in 140 patients

Published
2023
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41. Data from Epigenetic Inactivation of microRNA-34b/c Predicts Poor Disease-Free Survival in Early-Stage Lung Adenocarcinoma

Author

David G. Beer, Gabriel Capellà, Felipe Cardenal, Andrew C. Chang, Juan Moya, Ignacio Escobar, Roger Llatjos, Rishindra M. Reddy, Jules Lin, Zhuwen Wang, Anna Truini, Daysha Ferrer-Torres, Lin Lin, Marc Gallegos, Guoan Chen, and Ernest Nadal

Abstract

Purpose: The microRNA-34b/c (miR-34b/c) is considered a tumor suppressor in different tumor types and a transcriptional target of TP53. The main objectives of this study were to investigate the clinical implications of miR-34b/c methylation in patients with early-stage lung adenocarcinoma and to determine the functional role of miR-34b/c re-expression in lung adenocarcinoma cell lines.Experimental Design: Aberrant methylation and expression of miR-34b/c were assessed in 15 lung adenocarcinoma cell lines and a cohort of 140 early-stage lung adenocarcinoma. Lung adenocarcinoma cell lines were transfected with miR-34b/c and the effects upon cell proliferation, migration, invasion, and apoptosis were investigated.Results: Aberrant methylation of miR-34b/c was detected in 6 (40%) of 15 lung adenocarcinoma cell lines and 64 of 140 (46%) primary lung adenocarcinoma. Expression of miR-34b/c was significantly reduced in all methylated cell lines and primary tumors, especially with TP53 mutations. Patients with increased miR-34b/c methylation had significantly shorter disease-free and overall survival as compared to patients with unmethylated or low level of miR-34b/c methylation. Ectopic expression of miR-34b/c in lung adenocarcinoma cell lines decreased cell proliferation, migration, and invasion.Conclusions: Epigenetic inactivation of miR-34b/c by DNA methylation has independent prognostic value in patients with early-stage lung adenocarcinoma. Reexpression of miR-34b/c leads to a less aggressive phenotype in lung adenocarcinoma cell lines. Clin Cancer Res; 19(24); 6842–52. ©2013 AACR.

Published
2023
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42. Supplementary Materials and Methods from Molecular Landscape of Acquired Resistance to Targeted Therapy Combinations in BRAF-Mutant Colorectal Cancer

Author

Federica Di Nicolantonio, Ryan B. Corcoran, Salvatore Siena, Alberto Bardelli, Andrea Sartore-Bianchi, Jeffrey A. Engelman, Josep Tabernero, Jan H.M. Schellens, René Bernards, Margherita Gallicchio, Julieta Grasselli, Giulia Siravegna, Mauro Truini, Giorgio Corti, Michael Linnebacher, Carlotta Cancelliere, Michela Buscarino, Jason T. Godfrey, Valentina Boscaro, Giovanni Crisafulli, Alice Bartolini, Robin M.J.M. van Geel, Elena Elez, Giulia Marzolla, Genny Filiciotto, Andrea Cassingena, Sabrina Arena, Emanuele Valtorta, Ludovic Barault, Erin M. Sennott, and Daniele Oddo

Abstract

The file lists Supplementary Materials and Methods and relative References.

Published
2023
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43. Data from Molecular Landscape of Acquired Resistance to Targeted Therapy Combinations in BRAF-Mutant Colorectal Cancer

Author

Federica Di Nicolantonio, Ryan B. Corcoran, Salvatore Siena, Alberto Bardelli, Andrea Sartore-Bianchi, Jeffrey A. Engelman, Josep Tabernero, Jan H.M. Schellens, René Bernards, Margherita Gallicchio, Julieta Grasselli, Giulia Siravegna, Mauro Truini, Giorgio Corti, Michael Linnebacher, Carlotta Cancelliere, Michela Buscarino, Jason T. Godfrey, Valentina Boscaro, Giovanni Crisafulli, Alice Bartolini, Robin M.J.M. van Geel, Elena Elez, Giulia Marzolla, Genny Filiciotto, Andrea Cassingena, Sabrina Arena, Emanuele Valtorta, Ludovic Barault, Erin M. Sennott, and Daniele Oddo

Abstract

Although recent clinical trials of BRAF inhibitor combinations have demonstrated improved efficacy in BRAF-mutant colorectal cancer, emergence of acquired resistance limits clinical benefit. Here, we undertook a comprehensive effort to define mechanisms underlying drug resistance with the goal of guiding development of therapeutic strategies to overcome this limitation. We generated a broad panel of BRAF-mutant resistant cell line models across seven different clinically relevant drug combinations. Combinatorial drug treatments were able to abrogate ERK1/2 phosphorylation in parental-sensitive cells, but not in their resistant counterparts, indicating that resistant cells escaped drug treatments through one or more mechanisms leading to biochemical reactivation of the MAPK signaling pathway. Genotyping of resistant cells identified gene amplification of EGFR, KRAS, and mutant BRAF, as well as acquired mutations in KRAS, EGFR, and MAP2K1. These mechanisms were clinically relevant, as we identified emergence of a KRAS G12C mutation and increase of mutant BRAF V600E allele frequency in the circulating tumor DNA of a patient at relapse from combined treatment with BRAF and MEK inhibitors. To identify therapeutic combinations capable of overcoming drug resistance, we performed a systematic assessment of candidate therapies across the panel of resistant cell lines. Independent of the molecular alteration acquired upon drug pressure, most resistant cells retained sensitivity to vertical MAPK pathway suppression when combinations of ERK, BRAF, and EGFR inhibitors were applied. These therapeutic combinations represent promising strategies for future clinical trials in BRAF-mutant colorectal cancer. Cancer Res; 76(15); 4504–15. ©2016 AACR.

Published
2023
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44. Supplementary Figures and Tables from Molecular Landscape of Acquired Resistance to Targeted Therapy Combinations in BRAF-Mutant Colorectal Cancer

Author

Federica Di Nicolantonio, Ryan B. Corcoran, Salvatore Siena, Alberto Bardelli, Andrea Sartore-Bianchi, Jeffrey A. Engelman, Josep Tabernero, Jan H.M. Schellens, René Bernards, Margherita Gallicchio, Julieta Grasselli, Giulia Siravegna, Mauro Truini, Giorgio Corti, Michael Linnebacher, Carlotta Cancelliere, Michela Buscarino, Jason T. Godfrey, Valentina Boscaro, Giovanni Crisafulli, Alice Bartolini, Robin M.J.M. van Geel, Elena Elez, Giulia Marzolla, Genny Filiciotto, Andrea Cassingena, Sabrina Arena, Emanuele Valtorta, Ludovic Barault, Erin M. Sennott, and Daniele Oddo

Abstract

Supplementary Tables S1-S3 - List of drug concentrations to generate resistant cell lines (S1); Drug concentrations applied in the screening depicted in Figure 6 (S2); Primers for gene amplification and sequencing (S3). Supplementary Figure S1. Synergistic activity of targeted therapy combinations in BRAF mutant colorectal cancer cells. Supplementary Figure S2. Amplification of mutant BRAF V600E confers resistance to combined EGFR and MEK targeting in colorectal cancer cells. Supplemental Figure S3. Cytotoxicity induced by ERK inhibition in VACO432 resistant to BRAF combination therapies.

Published
2023
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46. Supplementary Figure Legends from Molecular Landscape of Acquired Resistance to Targeted Therapy Combinations in BRAF-Mutant Colorectal Cancer

Author

Federica Di Nicolantonio, Ryan B. Corcoran, Salvatore Siena, Alberto Bardelli, Andrea Sartore-Bianchi, Jeffrey A. Engelman, Josep Tabernero, Jan H.M. Schellens, René Bernards, Margherita Gallicchio, Julieta Grasselli, Giulia Siravegna, Mauro Truini, Giorgio Corti, Michael Linnebacher, Carlotta Cancelliere, Michela Buscarino, Jason T. Godfrey, Valentina Boscaro, Giovanni Crisafulli, Alice Bartolini, Robin M.J.M. van Geel, Elena Elez, Giulia Marzolla, Genny Filiciotto, Andrea Cassingena, Sabrina Arena, Emanuele Valtorta, Ludovic Barault, Erin M. Sennott, and Daniele Oddo

Abstract

Legends

Published
2023
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47. Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer

Author

Guoping Cai, Mary Ann Melnick, Anne C. Chiang, Ignacio Melero, Roy S. Herbst, Joseph Schlessinger, Weilai Dong, Richard P. Lifton, Ila Datar, David L. Rimm, Kurt A. Schalper, Anna Truini, Katerina Politi, Anna Wurtz, Soldano Ferrone, Luis M. Montuenga, Miguel F. Sanmamed, Scott N. Gettinger, Katherine Hastings, Sarah B. Goldberg, Victor Y. Du, Jungmin Choi, Jackeline Agorreta, Susan M. Kaech, Ryan T. Sowell, and Paula B. Kavathas

Subjects
0301 basic medicine, Lung Neoplasms, Human leukocyte antigen, Drug resistance, Biology, Article, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Interferon, medicine, Humans, Lung cancer, Antigen processing, Histocompatibility Antigens Class I, Cancer, medicine.disease, Gene Expression Regulation, Neoplastic, 030104 developmental biology, Oncology, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Immunology, biology.protein, Antibody, Signal Transduction, medicine.drug
Abstract

Mechanisms of acquired resistance to immune checkpoint inhibitors (ICI) are poorly understood. We leveraged a collection of 14 ICI-resistant lung cancer samples to investigate whether alterations in genes encoding HLA Class I antigen processing and presentation machinery (APM) components or interferon signaling play a role in acquired resistance to PD-1 or PD-L1 antagonistic antibodies. Recurrent mutations or copy-number changes were not detected in our cohort. In one case, we found acquired homozygous loss of B2M that caused lack of cell-surface HLA Class I expression in the tumor and a matched patient-derived xenograft (PDX). Downregulation of B2M was also found in two additional PDXs established from ICI-resistant tumors. CRISPR-mediated knockout of B2m in an immunocompetent lung cancer mouse model conferred resistance to PD-1 blockade in vivo, proving its role in resistance to ICIs. These results indicate that HLA Class I APM disruption can mediate escape from ICIs in lung cancer. Significance: As programmed death 1 axis inhibitors are becoming more established in standard treatment algorithms for diverse malignancies, acquired resistance to these therapies is increasingly being encountered. Here, we found that defective antigen processing and presentation can serve as a mechanism of such resistance in lung cancer. Cancer Discov; 7(12); 1420–35. ©2017 AACR. This article is highlighted in the In This Issue feature, p. 1355

Published
2017
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48. Tumor Heterogeneity and Lesion-Specific Response to Targeted Therapy in Colorectal Cancer

Author

Russo, Mariangela, Siravegna, Giulia, Blaszkowsky, Lawrence S., Corti, Giorgio, Crisafulli, Giovanni, Ahronian, Leanne G., Mussolin, Benedetta, Kwak, Eunice L., Buscarino, Michela, Lazzari, Luca, Valtorta, Emanuele, Truini, Mauro, Jessop, Nicholas A., Robinson, Hayley E., Hong, Theodore S., Mino Kenudson, Mari, DI NICOLANTONIO, Federica, Thabet, Ashraf, Sartore Bianchi, Andrea, Siena, Salvatore, Iafrate, John, Bardelli, Alberto, Corcoran, Ryan B., and joint co last authorshipjoint corresponding authorship

Subjects
0301 basic medicine, EGFR BLOCKADE, Colorectal cancer, medicine.medical_treatment, COLON CANCER, Bioinformatics, medicine.disease_cause, Metastasis, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, medicine, Panitumumab, Trametinib, Cetuximab, MUTATIONS, business.industry, MEK inhibitor, medicine.disease, Oncology, DRUG RESISTANCE, EGFR BLOCKADE, INTRATUMOR HETEROGENEITY, COLON CANCER, EVOLUTION, MUTATIONS, CETUXIMAB, EVOLUTION, CETUXIMAB, 3. Good health, DRUG RESISTANCE, 030104 developmental biology, Oncology, INTRATUMOR HETEROGENEITY, 030220 oncology & carcinogenesis, Cancer research, KRAS, business, medicine.drug
Abstract

How genomic heterogeneity associated with acquired resistance to targeted agents affects response to subsequent therapy is unknown. We studied EGFR blockade in colorectal cancer to assess whether tissue and liquid biopsies can be integrated with radiologic imaging to monitor the impact of individual oncogenic alterations on lesion-specific responses. Biopsy of a patient's progressing liver metastasis following prolonged response to cetuximab revealed a MEK1K57T mutation as a novel mechanism of acquired resistance. This lesion regressed upon treatment with panitumumab and the MEK inhibitor trametinib. In circulating tumor DNA (ctDNA), mutant MEK1 levels declined with treatment, but a previously unrecognized KRASQ61H mutation was also identified that increased despite therapy. This same KRAS mutation was later found in a separate nonresponding metastasis. In summary, parallel analyses of tumor biopsies and serial ctDNA monitoring show that lesion-specific radiographic responses to subsequent targeted therapies can be driven by distinct resistance mechanisms arising within separate tumor lesions in the same patient. Significance: Molecular heterogeneity ensuing from acquired resistance drives lesion-specific responses to subsequent targeted therapies. Analysis of a single-lesion biopsy is inadequate to guide selection of subsequent targeted therapies. ctDNA profiles allow the detection of concomitant resistance mechanisms residing in separate metastases and assessment of the effect of therapies designed to overcome resistance. Cancer Discov; 6(2); 147–53. ©2015 AACR. See related commentary by Hiley and Swanton, p. 122. This article is highlighted in the In This Issue feature, p. 109

Published
2016
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49. The EGFR Exon 19 Mutant L747-A750&gt;P Exhibits Distinct Sensitivity to Tyrosine Kinase Inhibitors in Lung Adenocarcinoma

Author

Truini, Anna, primary, Starrett, Jacqueline H., additional, Stewart, Tyler, additional, Ashtekar, Kumar, additional, Walther, Zenta, additional, Wurtz, Anna, additional, Lu, David, additional, Park, Jin H., additional, DeVeaux, Michelle, additional, Song, Xiaoling, additional, Gettinger, Scott, additional, Zelterman, Daniel, additional, Lemmon, Mark A., additional, Goldberg, Sarah B., additional, and Politi, Katerina, additional

Published
2019
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50. Combined Low Densities of FoxP3+ and CD3+ Tumor-Infiltrating Lymphocytes Identify Stage II Colorectal Cancer at High Risk of Progression

Author

Cavalleri, Tommaso, primary, Bianchi, Paolo, additional, Basso, Gianluca, additional, Celesti, Giuseppe, additional, Grizzi, Fabio, additional, Bossi, Paola, additional, Greco, Luana, additional, Pitrone, Calogero, additional, Valtorta, Emanuele, additional, Mauri, Gianluca, additional, Truini, Mauro, additional, Dall'Olio, Filippo Gustavo, additional, Brandi, Giovanni, additional, Sartore-Bianchi, Andrea, additional, Ricciardiello, Luigi, additional, Torri, Valter, additional, Rimassa, Lorenza, additional, Siena, Salvatore, additional, Mantovani, Alberto, additional, Malesci, Alberto, additional, and Laghi, Luigi, additional

Published
2019
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