Sarat Chandarlapaty
@saratchandarlapaty.bsky.social
📤 438
📥 312
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Physician Scientist, Medical Oncologist, My lab studies therapy resistance in breast cancer.
pinned post!
Published online today - work from our team led by Avantika Gupta, revealing how APOBEC3 mutagenesis promotes resistance to several targeted therapies in breast cancer. Check it out!
urldefense.com/v3/__https:/...
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APOBEC3 mutagenesis drives therapy resistance in breast cancer
Nature Genetics - Analysis of a large cohort of metastatic breast cancer samples shows that APOBEC mutational signatures are enriched in post-treatment samples. APOBEC activity was also associated...
https://urldefense.com/v3/__https://rdcu.be/emjaq__;!!KVWo1iE!WvNZ8mm-2M8SSRGbMJpzlqh5nKDm9b9xbwXp5vWS-OZj1lb7Ym1fKkDpdkhuxS-lwiHtWiA-BxYfHcpuinbMhB56WTffy0us$
6 months ago
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reposted by
Sarat Chandarlapaty
Elizabeth McKenna
1 day ago
Now online in Cancer Discovery
@aacrjournals.bsky.social
: Trastuzumab Deruxtecan (T-DXd) Resistance via Loss of HER2 Expression and Binding - by Wanyi Chen,
@joshdragomd.bsky.social
,
@saratchandarlapaty.bsky.social
, and colleagues
doi.org/10.1158/2159...
@mskcancercenter.bsky.social
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reposted by
Sarat Chandarlapaty
Josh Drago, MD, MS
1 day ago
ADC resistance is likely heterogeneous, and the phenomena above may explain only a portion of cases. But these early clues can inform prospective trail efforts, as well as ADC sequencing strategies. There is much more to come!
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reposted by
Sarat Chandarlapaty
Josh Drago, MD, MS
1 day ago
In this manuscript, online today in Cancer Discovery, we investigate target-mediated resistance to ADCs, and propose ways to overcome it.
aacrjournals.org/cancerdiscov...
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Trastuzumab Deruxtecan (T-DXd) Resistance via Loss of HER2 Expression and Binding
Abstract. T-DXd is clinically beneficial in HER2 positive and HER2 low metastatic breast cancer. However, therapeutic resistance emerges over time in most patients, with poorly defined resistance mech...
https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-25-0647/767191/Trastuzumab-Deruxtecan-T-DXd-Resistance-via-Loss
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Published online today - work led by Yanyan Cai: Inhibition of NR2F2 restores hormone therapy response to endocrine refractory breast cancers | Science Translational Medicine
www.science.org/doi/10.1126/...
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Inhibition of NR2F2 restores hormone therapy response to endocrine refractory breast cancers
NR2F2 modulates the ER cistrome, coregulator interactions, and chromatin accessibility to promote endocrine resistance in ER+ breast cancer.
https://www.science.org/doi/10.1126/scitranslmed.adk7786
5 months ago
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reposted by
Sarat Chandarlapaty
Memorial Sloan Kettering Cancer Center
6 months ago
🚨 NEW in
@natgenet.nature.com
: MSK's Dr. Sarat Chandarlapaty and colleagues investigates how APOBEC3
#mutagenesis
drives therapy resistance in
#BreastCancer
. Learn more:
www.nature.com/articles/s41...
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reposted by
Sarat Chandarlapaty
Avantika Gupta
6 months ago
So excited to share our latest work with
@saratchandarlapaty.bsky.social
, Antonio Marra, Andrea Gazzo
@mskcancercenter.bsky.social
out today in
@natgenet.nature.com
! We uncover the function and mechanism of APOBEC3-driven therapy resistance in breast cancer. 🧵 1/
www.nature.com/articles/s41...
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APOBEC3 mutagenesis drives therapy resistance in breast cancer - Nature Genetics
Analysis of a large cohort of metastatic breast cancer samples shows that APOBEC mutational signatures are enriched in post-treatment samples. APOBEC activity was also associated with mutations known ...
https://www.nature.com/articles/s41588-025-02187-1
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Published online today - work from our team led by Avantika Gupta, revealing how APOBEC3 mutagenesis promotes resistance to several targeted therapies in breast cancer. Check it out!
urldefense.com/v3/__https:/...
loading . . .
APOBEC3 mutagenesis drives therapy resistance in breast cancer
Nature Genetics - Analysis of a large cohort of metastatic breast cancer samples shows that APOBEC mutational signatures are enriched in post-treatment samples. APOBEC activity was also associated...
https://urldefense.com/v3/__https://rdcu.be/emjaq__;!!KVWo1iE!WvNZ8mm-2M8SSRGbMJpzlqh5nKDm9b9xbwXp5vWS-OZj1lb7Ym1fKkDpdkhuxS-lwiHtWiA-BxYfHcpuinbMhB56WTffy0us$
6 months ago
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reposted by
Sarat Chandarlapaty
Avantika Gupta
7 months ago
@saratchandarlapaty.bsky.social
expertly summarizing our work on how underlying genomic instability in breast cancer leads to therapy resistance leaving with key ideas on how we might target them! Come see me expand on the role of APOBEC3 mutagenesis in these processes tomorrow morning at
#AACR25
!
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reposted by
Sarat Chandarlapaty
Avantika Gupta
11 months ago
A hugely collaborative team effort under the mentorship of
@saratchandarlapaty.bsky.social
@mskcancercenter.bsky.social
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Fabulous plenary from Dr. Pedram Razavi
#sabcs2024
on robust and innovative ai models to separate cdk4/6i responders from non-responders.
11 months ago
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Fantastic presentation
#SABCS
by
@avantikagupta.bsky.social
on apobec3 in breast cancer. Demonstrating the role of this process in promoting therapy resistance.
11 months ago
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reposted by
Sarat Chandarlapaty
Avantika Gupta
11 months ago
Congratulations to
@caiy0219.bsky.social
for an excellent poster presentation today! 👏🏽 Also, so happy to be reunited with
@reikudo.bsky.social
to represent the translational team in
@saratchandarlapaty.bsky.social
’s lab at
#SABCS2024
!
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Super plenary from Komal Jhaveri on imlunestrant
#sabcs
Congrats to her and the Ember-3 trial authors for developing this SERD (and combo with Abema)
11 months ago
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reposted by
Sarat Chandarlapaty
Tatiana Prowell, MD
12 months ago
NEW
#Oncology
: EGFR expression mediates resistance to T-DXd (EGFR overexpression ⬇️ HER2 homodimerization & HER2/ADC internalization) Combining with EGFR mAbs restored HER2/ADC trafficking & ⬆️ activity in nonclinical models
#DrugDevelopment
#OncoSky
www.cell.com/cell-reports...
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EGFR-directed antibodies promote HER2 ADC internalization and efficacy
Gupta et al. demonstrate that high EGFR expression mediates resistance to HER2 antibody drug conjugates (ADCs) including trastuzumab deruxtecan (T-DXd) by limiting HER2/ADC internalization. The additi...
https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(24)00539-1
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