Thread by @TumorBoardTues

#TBTWebinar w/ @MPishvaian, @PancPathologist, @BreastCancerMD1, & Emanuel Petricoin

#CME🔗 bit.ly/3E7Crgu
Pretest bit.ly/3lkw2r0
Claim credit bit.ly/3ljVVXM

Supported by AstraZeneca Pharmaceuticals & Daiichi Sankyo, Inc.

twitter.com/i/broadcasts/1…

#TumorBoardTuesday
HER2 #TBTWebinar 🔑

HER2 (ERBB2) is frequently altered in cancer
(Breast, Lung, Gastric, Biliary, CRC)

Marked by⬆️expression from🧬amplification

Also⬆️activity due to a🌟constitutively active🧬mutation

🤔1⃣of a few🎯molecular drivers of aggressive cancer

#TumorBoardTuesday
HER2 #TBTWebinar 🧐

➡️HER2 (ERBB2) testing & cut-offs varies between disease types

➡️IHC, FISH/CISH, & NGS can be used

➡️🧐Importantly, even HER2-low expression tumors may still benefit from emerging HER2-targeted antibody-drug conjugates🎯

#TumorBoardTuesday
HER2 #TBTWebinar 🔑

➡️HER2 & HER3 dimerization is a driver of aggressive tumors
✅Ligand dependent (NRG)
✅Ligand independent HER2 autoactivation
➡️Activates downstream oncogenic signaling
✅PI3K/AKT
✅MEK/MAPK
✅JAK/STAT
➡️Mediates💊resistance mechanisms⚙️

#TumorBoardTuesday
HER2 #TBTWebinar 🔑

➡️HER2 activity requires receptor dimerization

➡️HER2 is the preferred interacting partner of:

✅EGFR in aggressive 🫁 adenocarcinoma
✅HER3 in breast & ovarian cancers

➡️🧐HER2 testing may also include HER2 phosphorylation (RPPA)

#TumorBoardTuesday
HER2 #TBTWebinar🔑
➡️MOA Targeted Agents🎯
✅Anti-HER2, eg, trastuzumab🚫signaling
✅Anti-HER2, eg, pertuzumab🚫dimerization
✅Antibody-drug conjugate (ADC), eg, T-DM1 intracellular cytotoxic💊delivery
✅Tyrosine kinase (TK) inhibitor, eg, neratinib🚫activity

#TumorBoardTuesday
HER2 #TBTWebinar 🎀

➡️HER2🔬is👏in many cancers

➡️Alterations include⬆️protein, ⬆️🧬amplification, & constitutive activation🌟

➡️HER2➕cancers are aggressive but🎯💊includes antibodies, TKIs & ADCs

➡️HER3 dimerizes w/HER2➡️potent driver of Tx resistance🤔