Sarat Chandarlapaty

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

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!

In this manuscript, online today in Cancer Discovery, we investigate target-mediated resistance to ADCs, and propose ways to overcome it.

aacrjournals.org/cancerdiscov...

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.

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/...

🚨 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...

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 ...

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...

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...

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:/...

@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!

A hugely collaborative team effort under the mentorship of @saratchandarlapaty.bsky.social @mskcancercenter.bsky.social

Fabulous plenary from Dr. Pedram Razavi #sabcs2024 on robust and innovative ai models to separate cdk4/6i responders from non-responders.

Fantastic presentation #SABCS by @avantikagupta.bsky.social on apobec3 in breast cancer. Demonstrating the role of this process in promoting therapy resistance.

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!

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)

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...

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...