Search

Your search keyword '"Chadalavada, Kalyani"' showing total 20 results
Start Over Author "Chadalavada, Kalyani" Publication Year Range Last 3 years
20 results on '"Chadalavada, Kalyani"'

1. Ordered and deterministic cancer genome evolution after p53 loss

Author

Baslan, Timour, Morris, IV, John P., Zhao, Zhen, Reyes, Jose, Ho, Yu-Jui, Tsanov, Kaloyan M., Bermeo, Jonathan, Tian, Sha, Zhang, Sean, Askan, Gokce, Yavas, Aslihan, Lecomte, Nicolas, Erakky, Amanda, Varghese, Anna M., Zhang, Amy, Kendall, Jude, Ghiban, Elena, Chorbadjiev, Lubomir, Wu, Jie, Dimitrova, Nevenka, Chadalavada, Kalyani, Nanjangud, Gouri J., Bandlamudi, Chaitanya, Gong, Yixiao, Donoghue, Mark T. A., Socci, Nicholas D., Krasnitz, Alex, Notta, Faiyaz, Leach, Steve D., Iacobuzio-Donahue, Christine A., and Lowe, Scott W.

Published
2022
Full Text
View/download PDF

3. Quantifying Y chromosome loss in primary and metastatic prostate cancer by chromosome painting.

Author

Rajanala, Sai Harisha, Ghale, Romina, Nandakumar, Subhiksha, Chadalavada, Kalyani, Lee, Gwo-Shu Mary, Stopsack, Konrad H., Chen, Yu, Nanjangud, Gouri J., Chakraborty, Goutam, and Kantoff, Philip W.

Subjects
Y chromosome, CASTRATION-resistant prostate cancer, PROSTATE cancer, METASTASIS, CHROMOSOMES, NUDITY
Abstract

Somatic Y chromosome loss in hematopoietic cells is associated with higher mortality in men. However, the status of the Y chromosome in cancer tissue is not fully known due to technical limitations, such as difficulties in labelling and sequencing DNA from the Y chromosome. We have developed a system to quantify Y chromosome gain or loss in patient-derived prostate cancer organoids. Using our system, we observed Y chromosome loss in 4 of the 13 (31%) patient-derived metastatic castration-resistant prostate cancer (mCRPC) organoids; interestingly, loss of Yq (long arm of the Y chromosome) was seen in 38% of patient-derived organoids. Additionally, potential associations were observed between mCRPC and Y chromosome nullisomy. The prevalence of Y chromosome loss was similar in primary and metastatic tissue, suggesting that Y chromosome loss is an early event in prostate cancer evolution and may not a result of drug resistance or organoid derivation. This study reports quantification of Y chromosome loss and gain in primary and metastatic prostate cancer tissue and lays the groundwork for further studies investigating the clinical relevance of Y chromosome loss or gain in mCRPC. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

4. Supplementary Table 1 from Molecular Characterization of Acquired Resistance to KRASG12C–EGFR Inhibition in Colorectal Cancer

Author

Yaeger, Rona, primary, Mezzadra, Riccardo, primary, Sinopoli, Jenna, primary, Bian, Yu, primary, Marasco, Michelangelo, primary, Kaplun, Esther, primary, Gao, Yijun, primary, Zhao, HuiYong, primary, Paula, Arnaud Da Cruz, primary, Zhu, Yingjie, primary, Perez, Almudena Chaves, primary, Chadalavada, Kalyani, primary, Tse, Edison, primary, Chowdhry, Sudhir, primary, Bowker, Sydney, primary, Chang, Qing, primary, Qeriqi, Besnik, primary, Weigelt, Britta, primary, Nanjangud, Gouri J., primary, Berger, Michael F., primary, Der-Torossian, Hirak, primary, Anderes, Kenna, primary, Socci, Nicholas D., primary, Shia, Jinru, primary, Riely, Gregory J., primary, Murciano-Goroff, Yonina R., primary, Li, Bob T., primary, Christensen, James G., primary, Reis-Filho, Jorge S., primary, Solit, David B., primary, de Stanchina, Elisa, primary, Lowe, Scott W., primary, Rosen, Neal, primary, and Misale, Sandra, primary

Published
2023
Full Text
View/download PDF

5. Supplementary Table 2 from Molecular Characterization of Acquired Resistance to KRASG12C–EGFR Inhibition in Colorectal Cancer

Author

Yaeger, Rona, primary, Mezzadra, Riccardo, primary, Sinopoli, Jenna, primary, Bian, Yu, primary, Marasco, Michelangelo, primary, Kaplun, Esther, primary, Gao, Yijun, primary, Zhao, HuiYong, primary, Paula, Arnaud Da Cruz, primary, Zhu, Yingjie, primary, Perez, Almudena Chaves, primary, Chadalavada, Kalyani, primary, Tse, Edison, primary, Chowdhry, Sudhir, primary, Bowker, Sydney, primary, Chang, Qing, primary, Qeriqi, Besnik, primary, Weigelt, Britta, primary, Nanjangud, Gouri J., primary, Berger, Michael F., primary, Der-Torossian, Hirak, primary, Anderes, Kenna, primary, Socci, Nicholas D., primary, Shia, Jinru, primary, Riely, Gregory J., primary, Murciano-Goroff, Yonina R., primary, Li, Bob T., primary, Christensen, James G., primary, Reis-Filho, Jorge S., primary, Solit, David B., primary, de Stanchina, Elisa, primary, Lowe, Scott W., primary, Rosen, Neal, primary, and Misale, Sandra, primary

Published
2023
Full Text
View/download PDF

6. Supplementary Figure 6 from Molecular Characterization of Acquired Resistance to KRASG12C–EGFR Inhibition in Colorectal Cancer

Author

Yaeger, Rona, primary, Mezzadra, Riccardo, primary, Sinopoli, Jenna, primary, Bian, Yu, primary, Marasco, Michelangelo, primary, Kaplun, Esther, primary, Gao, Yijun, primary, Zhao, HuiYong, primary, Paula, Arnaud Da Cruz, primary, Zhu, Yingjie, primary, Perez, Almudena Chaves, primary, Chadalavada, Kalyani, primary, Tse, Edison, primary, Chowdhry, Sudhir, primary, Bowker, Sydney, primary, Chang, Qing, primary, Qeriqi, Besnik, primary, Weigelt, Britta, primary, Nanjangud, Gouri J., primary, Berger, Michael F., primary, Der-Torossian, Hirak, primary, Anderes, Kenna, primary, Socci, Nicholas D., primary, Shia, Jinru, primary, Riely, Gregory J., primary, Murciano-Goroff, Yonina R., primary, Li, Bob T., primary, Christensen, James G., primary, Reis-Filho, Jorge S., primary, Solit, David B., primary, de Stanchina, Elisa, primary, Lowe, Scott W., primary, Rosen, Neal, primary, and Misale, Sandra, primary

Published
2023
Full Text
View/download PDF

7. Supplementary Figure 3 from Molecular Characterization of Acquired Resistance to KRASG12C–EGFR Inhibition in Colorectal Cancer

Author

Yaeger, Rona, primary, Mezzadra, Riccardo, primary, Sinopoli, Jenna, primary, Bian, Yu, primary, Marasco, Michelangelo, primary, Kaplun, Esther, primary, Gao, Yijun, primary, Zhao, HuiYong, primary, Paula, Arnaud Da Cruz, primary, Zhu, Yingjie, primary, Perez, Almudena Chaves, primary, Chadalavada, Kalyani, primary, Tse, Edison, primary, Chowdhry, Sudhir, primary, Bowker, Sydney, primary, Chang, Qing, primary, Qeriqi, Besnik, primary, Weigelt, Britta, primary, Nanjangud, Gouri J., primary, Berger, Michael F., primary, Der-Torossian, Hirak, primary, Anderes, Kenna, primary, Socci, Nicholas D., primary, Shia, Jinru, primary, Riely, Gregory J., primary, Murciano-Goroff, Yonina R., primary, Li, Bob T., primary, Christensen, James G., primary, Reis-Filho, Jorge S., primary, Solit, David B., primary, de Stanchina, Elisa, primary, Lowe, Scott W., primary, Rosen, Neal, primary, and Misale, Sandra, primary

Published
2023
Full Text
View/download PDF

8. Supplementary Figure 4 from Molecular Characterization of Acquired Resistance to KRASG12C–EGFR Inhibition in Colorectal Cancer

Author

Yaeger, Rona, primary, Mezzadra, Riccardo, primary, Sinopoli, Jenna, primary, Bian, Yu, primary, Marasco, Michelangelo, primary, Kaplun, Esther, primary, Gao, Yijun, primary, Zhao, HuiYong, primary, Paula, Arnaud Da Cruz, primary, Zhu, Yingjie, primary, Perez, Almudena Chaves, primary, Chadalavada, Kalyani, primary, Tse, Edison, primary, Chowdhry, Sudhir, primary, Bowker, Sydney, primary, Chang, Qing, primary, Qeriqi, Besnik, primary, Weigelt, Britta, primary, Nanjangud, Gouri J., primary, Berger, Michael F., primary, Der-Torossian, Hirak, primary, Anderes, Kenna, primary, Socci, Nicholas D., primary, Shia, Jinru, primary, Riely, Gregory J., primary, Murciano-Goroff, Yonina R., primary, Li, Bob T., primary, Christensen, James G., primary, Reis-Filho, Jorge S., primary, Solit, David B., primary, de Stanchina, Elisa, primary, Lowe, Scott W., primary, Rosen, Neal, primary, and Misale, Sandra, primary

Published
2023
Full Text
View/download PDF

9. Supplementary Figure 5 from Molecular Characterization of Acquired Resistance to KRASG12C–EGFR Inhibition in Colorectal Cancer

Author

Yaeger, Rona, primary, Mezzadra, Riccardo, primary, Sinopoli, Jenna, primary, Bian, Yu, primary, Marasco, Michelangelo, primary, Kaplun, Esther, primary, Gao, Yijun, primary, Zhao, HuiYong, primary, Paula, Arnaud Da Cruz, primary, Zhu, Yingjie, primary, Perez, Almudena Chaves, primary, Chadalavada, Kalyani, primary, Tse, Edison, primary, Chowdhry, Sudhir, primary, Bowker, Sydney, primary, Chang, Qing, primary, Qeriqi, Besnik, primary, Weigelt, Britta, primary, Nanjangud, Gouri J., primary, Berger, Michael F., primary, Der-Torossian, Hirak, primary, Anderes, Kenna, primary, Socci, Nicholas D., primary, Shia, Jinru, primary, Riely, Gregory J., primary, Murciano-Goroff, Yonina R., primary, Li, Bob T., primary, Christensen, James G., primary, Reis-Filho, Jorge S., primary, Solit, David B., primary, de Stanchina, Elisa, primary, Lowe, Scott W., primary, Rosen, Neal, primary, and Misale, Sandra, primary

Published
2023
Full Text
View/download PDF

10. Supplementary Figure 1 from Molecular Characterization of Acquired Resistance to KRASG12C–EGFR Inhibition in Colorectal Cancer

Author

Yaeger, Rona, primary, Mezzadra, Riccardo, primary, Sinopoli, Jenna, primary, Bian, Yu, primary, Marasco, Michelangelo, primary, Kaplun, Esther, primary, Gao, Yijun, primary, Zhao, HuiYong, primary, Paula, Arnaud Da Cruz, primary, Zhu, Yingjie, primary, Perez, Almudena Chaves, primary, Chadalavada, Kalyani, primary, Tse, Edison, primary, Chowdhry, Sudhir, primary, Bowker, Sydney, primary, Chang, Qing, primary, Qeriqi, Besnik, primary, Weigelt, Britta, primary, Nanjangud, Gouri J., primary, Berger, Michael F., primary, Der-Torossian, Hirak, primary, Anderes, Kenna, primary, Socci, Nicholas D., primary, Shia, Jinru, primary, Riely, Gregory J., primary, Murciano-Goroff, Yonina R., primary, Li, Bob T., primary, Christensen, James G., primary, Reis-Filho, Jorge S., primary, Solit, David B., primary, de Stanchina, Elisa, primary, Lowe, Scott W., primary, Rosen, Neal, primary, and Misale, Sandra, primary

Published
2023
Full Text
View/download PDF

11. Supplementary Figure 2 from Molecular Characterization of Acquired Resistance to KRASG12C–EGFR Inhibition in Colorectal Cancer

Author

Yaeger, Rona, primary, Mezzadra, Riccardo, primary, Sinopoli, Jenna, primary, Bian, Yu, primary, Marasco, Michelangelo, primary, Kaplun, Esther, primary, Gao, Yijun, primary, Zhao, HuiYong, primary, Paula, Arnaud Da Cruz, primary, Zhu, Yingjie, primary, Perez, Almudena Chaves, primary, Chadalavada, Kalyani, primary, Tse, Edison, primary, Chowdhry, Sudhir, primary, Bowker, Sydney, primary, Chang, Qing, primary, Qeriqi, Besnik, primary, Weigelt, Britta, primary, Nanjangud, Gouri J., primary, Berger, Michael F., primary, Der-Torossian, Hirak, primary, Anderes, Kenna, primary, Socci, Nicholas D., primary, Shia, Jinru, primary, Riely, Gregory J., primary, Murciano-Goroff, Yonina R., primary, Li, Bob T., primary, Christensen, James G., primary, Reis-Filho, Jorge S., primary, Solit, David B., primary, de Stanchina, Elisa, primary, Lowe, Scott W., primary, Rosen, Neal, primary, and Misale, Sandra, primary

Published
2023
Full Text
View/download PDF

12. Supplementary Table 3 from Molecular Characterization of Acquired Resistance to KRASG12C–EGFR Inhibition in Colorectal Cancer

Author

Yaeger, Rona, primary, Mezzadra, Riccardo, primary, Sinopoli, Jenna, primary, Bian, Yu, primary, Marasco, Michelangelo, primary, Kaplun, Esther, primary, Gao, Yijun, primary, Zhao, HuiYong, primary, Paula, Arnaud Da Cruz, primary, Zhu, Yingjie, primary, Perez, Almudena Chaves, primary, Chadalavada, Kalyani, primary, Tse, Edison, primary, Chowdhry, Sudhir, primary, Bowker, Sydney, primary, Chang, Qing, primary, Qeriqi, Besnik, primary, Weigelt, Britta, primary, Nanjangud, Gouri J., primary, Berger, Michael F., primary, Der-Torossian, Hirak, primary, Anderes, Kenna, primary, Socci, Nicholas D., primary, Shia, Jinru, primary, Riely, Gregory J., primary, Murciano-Goroff, Yonina R., primary, Li, Bob T., primary, Christensen, James G., primary, Reis-Filho, Jorge S., primary, Solit, David B., primary, de Stanchina, Elisa, primary, Lowe, Scott W., primary, Rosen, Neal, primary, and Misale, Sandra, primary

Published
2023
Full Text
View/download PDF

13. Data from Molecular Characterization of Acquired Resistance to KRASG12C–EGFR Inhibition in Colorectal Cancer

Author

Yaeger, Rona, primary, Mezzadra, Riccardo, primary, Sinopoli, Jenna, primary, Bian, Yu, primary, Marasco, Michelangelo, primary, Kaplun, Esther, primary, Gao, Yijun, primary, Zhao, HuiYong, primary, Paula, Arnaud Da Cruz, primary, Zhu, Yingjie, primary, Perez, Almudena Chaves, primary, Chadalavada, Kalyani, primary, Tse, Edison, primary, Chowdhry, Sudhir, primary, Bowker, Sydney, primary, Chang, Qing, primary, Qeriqi, Besnik, primary, Weigelt, Britta, primary, Nanjangud, Gouri J., primary, Berger, Michael F., primary, Der-Torossian, Hirak, primary, Anderes, Kenna, primary, Socci, Nicholas D., primary, Shia, Jinru, primary, Riely, Gregory J., primary, Murciano-Goroff, Yonina R., primary, Li, Bob T., primary, Christensen, James G., primary, Reis-Filho, Jorge S., primary, Solit, David B., primary, de Stanchina, Elisa, primary, Lowe, Scott W., primary, Rosen, Neal, primary, and Misale, Sandra, primary

Published
2023
Full Text
View/download PDF

14. Table S8 from Significance of BRCA2 and RB1 Co-loss in Aggressive Prostate Cancer Progression

Author

Chakraborty, Goutam, primary, Armenia, Joshua, primary, Mazzu, Ying Z., primary, Nandakumar, Subhiksha, primary, Stopsack, Konrad H., primary, Atiq, Mohammad O., primary, Komura, Kazumasa, primary, Jehane, Lina, primary, Hirani, Rahim, primary, Chadalavada, Kalyani, primary, Yoshikawa, Yuki, primary, Khan, Nabeela A., primary, Chen, Yu, primary, Abida, Wassim, primary, Mucci, Lorelei A., primary, Lee, Gwo-Shu Mary, primary, Nanjangud, Gouri J., primary, and Kantoff, Philip W., primary

Published
2023
Full Text
View/download PDF

15. Figure S2 from Significance of BRCA2 and RB1 Co-loss in Aggressive Prostate Cancer Progression

Author

Chakraborty, Goutam, primary, Armenia, Joshua, primary, Mazzu, Ying Z., primary, Nandakumar, Subhiksha, primary, Stopsack, Konrad H., primary, Atiq, Mohammad O., primary, Komura, Kazumasa, primary, Jehane, Lina, primary, Hirani, Rahim, primary, Chadalavada, Kalyani, primary, Yoshikawa, Yuki, primary, Khan, Nabeela A., primary, Chen, Yu, primary, Abida, Wassim, primary, Mucci, Lorelei A., primary, Lee, Gwo-Shu Mary, primary, Nanjangud, Gouri J., primary, and Kantoff, Philip W., primary

Published
2023
Full Text
View/download PDF

16. Molecular Characterization of Acquired Resistance to KRASG12C-EGFR Inhibition in Colorectal Cancer

Author

Yaeger, Rona, primary, Mezzadra, Riccardo, additional, Sinopoli, Jenna, additional, Bian, Yu, additional, Marasco, Michelangelo, additional, Kaplun, Esther, additional, Gao, Yijun, additional, Zhao, HuiYong, additional, Paula, Arnaud Da Cruz, additional, Zhu, Yingjie, additional, Perez, Almudena Chaves, additional, Chadalavada, Kalyani, additional, Tse, Edison, additional, Chowdhry, Sudhir, additional, Bowker, Sydney, additional, Chang, Qing, additional, Qeriqi, Besnik, additional, Weigelt, Britta, additional, Nanjangud, Gouri J., additional, Berger, Michael F., additional, Der-Torossian, Hirak, additional, Anderes, Kenna, additional, Socci, Nicholas D., additional, Shia, Jinru, additional, Riely, Gregory J., additional, Murciano-Goroff, Yonina R., additional, Li, Bob T., additional, Christensen, James G., additional, Reis-Filho, Jorge S., additional, Solit, David B., additional, de Stanchina, Elisa, additional, Lowe, Scott W., additional, Rosen, Neal, additional, and Misale, Sandra, additional

Published
2022
Full Text
View/download PDF

17. Error-prone repair of stalled replication forks drives mutagenesis and loss of heterozygosity in haploinsufficient BRCA1 cells

Author

Deshpande, Madhura, primary, Paniza, Theodore, additional, Jalloul, Nahed, additional, Nanjangud, Gouri, additional, Twarowski, Jerzy, additional, Koren, Amnon, additional, Zaninovic, Nikica, additional, Zhan, Qiansheng, additional, Chadalavada, Kalyani, additional, Malkova, Anna, additional, Khiabanian, Hossein, additional, Madireddy, Advaitha, additional, Rosenwaks, Zev, additional, and Gerhardt, Jeannine, additional

Published
2022
Full Text
View/download PDF

18. TERT Copy Number Alterations, Promoter Mutations and Rearrangements in Adrenocortical Carcinomas

Author

Gupta, Sounak, primary, Won, Helen, additional, Chadalavada, Kalyani, additional, Nanjangud, Gouri J., additional, Chen, Ying-Bei, additional, Al-Ahmadie, Hikmat A., additional, Fine, Samson W., additional, Sirintrapun, Sahussapont J., additional, Strong, Vivian E., additional, Raj, Nitya, additional, Lagunes, Diane Reidy, additional, Vanderbilt, Chad M., additional, Berger, Michael F., additional, Ladanyi, Marc, additional, Dogan, Snjezana, additional, Tickoo, Satish K., additional, Reuter, Victor E., additional, and Gopalan, Anuradha, additional

Published
2021
Full Text
View/download PDF

19. Molecular and Clinical Determinants of Acquired Resistance and Treatment Duration for Targeted Therapies in Colorectal Cancer.

Author

Harrold E, Keane F, Walch H, Chou JF, Sinopoli J, Palladino S, Al-Rawi DH, Chadalavada K, Manca P, Chalasani S, Yang J, Cercek A, Shia J, Capanu M, Bakhoum SF, Schultz N, Chatila WK, and Yaeger R

Subjects
Humans, Female, Male, Middle Aged, Aged, Proto-Oncogene Proteins p21(ras) genetics, Receptor, ErbB-2 genetics, Receptor, ErbB-2 metabolism, Mutation, Disease Progression, ErbB Receptors genetics, ErbB Receptors antagonists & inhibitors, Adult, Chromosomal Instability, Aged, 80 and over, Gene Amplification, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Colorectal Neoplasms drug therapy, Drug Resistance, Neoplasm genetics, Molecular Targeted Therapy, Proto-Oncogene Proteins B-raf genetics
Abstract

Purpose: Targeted therapies have improved outcomes for patients with metastatic colorectal cancer, but their impact is limited by rapid emergence of resistance. We hypothesized that an understanding of the underlying genetic mechanisms and intrinsic tumor features that mediate resistance to therapy will guide new therapeutic strategies and ultimately allow the prevention of resistance., Experimental Design: We assembled a series of 52 patients with paired pretreatment and progression samples who received therapy targeting EGFR (n = 17), BRAF V600E (n = 17), KRAS G12C (n = 15), or amplified HER2 (n = 3) to identify molecular and clinical factors associated with time on treatment (TOT)., Results: All patients stopped treatment for progression and TOT did not vary by oncogenic driver (P = 0.5). Baseline disease burden (≥3 vs. <3 sites, P = 0.02), the presence of hepatic metastases (P = 0.02), and gene amplification on baseline tissue (P = 0.03) were each associated with shorter TOT. We found evidence of chromosomal instability (CIN) at progression in patients with baseline MAPK pathway amplifications and those with acquired gene amplifications. At resistance, copy-number changes (P = 0.008) and high number (≥5) of acquired alterations (P = 0.04) were associated with shorter TOT. Patients with hepatic metastases demonstrated both higher number of emergent alterations at resistance and enrichment of mutations involving receptor tyrosine kinases., Conclusions: Our genomic analysis suggests that high baseline CIN or effective induction of enhanced mutagenesis on targeted therapy underlies rapid progression. Longer response appears to result from a progressive acquisition of genomic or chromosomal instability in the underlying cancer or from the chance event of a new resistance alteration., (©2024 The Authors; Published by the American Association for Cancer Research.)

Published
2024
Full Text
View/download PDF

20. Molecular Characterization of Acquired Resistance to KRASG12C-EGFR Inhibition in Colorectal Cancer.

Author

Yaeger R, Mezzadra R, Sinopoli J, Bian Y, Marasco M, Kaplun E, Gao Y, Zhao H, Paula ADC, Zhu Y, Perez AC, Chadalavada K, Tse E, Chowdhry S, Bowker S, Chang Q, Qeriqi B, Weigelt B, Nanjangud GJ, Berger MF, Der-Torossian H, Anderes K, Socci ND, Shia J, Riely GJ, Murciano-Goroff YR, Li BT, Christensen JG, Reis-Filho JS, Solit DB, de Stanchina E, Lowe SW, Rosen N, and Misale S

Subjects
Animals, Humans, Signal Transduction, Disease Models, Animal, ErbB Receptors, Proto-Oncogene Proteins p21(ras) genetics, Proto-Oncogene Proteins p21(ras) metabolism, Mutation, Drug Resistance, Neoplasm genetics, Colorectal Neoplasms drug therapy, Colorectal Neoplasms genetics, Colorectal Neoplasms metabolism
Abstract

With the combination of KRASG12C and EGFR inhibitors, KRAS is becoming a druggable target in colorectal cancer. However, secondary resistance limits its efficacy. Using cell lines, patient-derived xenografts, and patient samples, we detected a heterogeneous pattern of putative resistance alterations expected primarily to prevent inhibition of ERK signaling by drugs at progression. Serial analysis of patient blood samples on treatment demonstrates that most of these alterations are detected at a low frequency except for KRASG12C amplification, a recurrent resistance mechanism that rises in step with clinical progression. Upon drug withdrawal, resistant cells with KRASG12C amplification undergo oncogene-induced senescence, and progressing patients experience a rapid fall in levels of this alteration in circulating DNA. In this new state, drug resumption is ineffective as mTOR signaling is elevated. However, our work exposes a potential therapeutic vulnerability, whereby therapies that target the senescence response may overcome acquired resistance., Significance: Clinical resistance to KRASG12C-EGFR inhibition primarily prevents suppression of ERK signaling. Most resistance mechanisms are subclonal, whereas KRASG12C amplification rises over time to drive a higher portion of resistance. This recurrent resistance mechanism leads to oncogene-induced senescence upon drug withdrawal and creates a potential vulnerability to senolytic approaches. This article is highlighted in the In This Issue feature, p. 1., (©2022 The Authors; Published by the American Association for Cancer Research.)

Published
2023
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results