Maria F Teixeira

1/n Daraxonrasib (RMC-6236), the first-in-human oral 💊RAS(ON) multi-selective tri-complex inhibitor, in previously treated RAS-mutated pancreatic cancer phase I/II study is now published in the New England Journal of Medicine @NEJM A novel💡 way to shut down ⚔️RAS, one of the most important oncogenic drivers in cancer that had long been considered “undruggable.” 🔗nejm.org/doi/full/10.10… Shout out to Brian Wolpin, @CentralParkWMD @GarridoLagunaMD @AlexSpiraMDPhD @salmanpunekar @MeredithPelster @bherzbergmd Nilo Azad Aparna Hegde @DavidHongMD and the whole team who dedicated to this study. @EileenMOReilly #HBP #HumansBeyondPatients

#AACR26 highlights #CommunityOnc: 1. #CM77T: PeriOP/PostOP Nivo in NSCLC 2. #TRUST: ROS1 1L NSCLC 3. RAS Inhibitor - Zoldonrasib in 2L and beyond NSCLC 4. RAS Inhibitor in Panc Ca - Daraxonrasib monotherapy in 1 L - Daraxonrasib + chemo in 1L #OncTwitter #MedX 1/6

RevMed with huge news for pancreatic cancer (daraxonrasib). The headline is hard to ignore 👀 • Median OS 13.2 vs 6.7 months • HR ~0.4 📉 • Activity across KRAS variants (not just G12C) • Manageable safety If that signal is real, this isn’t incremental. It changes how we think about KRAS. But—caveat applies ⚠️ This is a press release! PR as a rule is rosier than real data. Still… an OS HR like that gets your attention. Feels like we may be moving from mutation-specific inhibition → broader KRAS control. That’s the difference between niche utility and something that touches CRC, pancreas, lung… everything we see. Now we wait for the data behind the headline. @TheGutOncLab @OncoAlert @Onco_Nexus ir.revmed.com/news-releases/…

🚨 Up to 40% of rectal cancer patients may not need surgery. In dMMR disease (with proper testing) Immunotherapy → ~90-100% CR In MSS TNT: ~1 in 3 achieve cCR With watch-and-wait: ~85% keep their rectum >95% remain metastasis-free Local regrowth ~15%, mostly detected early and successfully salvaged It’s smarter upfront intensification then personalized decisions. But this isn’t a simple algorithm. It requires clinical judgment, proper testing, careful selection and intensive surveillance. What once seemed unthinkable is now part of evolving clinical practice; the state of the art care thelancet.com/journals/eclin…

@pashtoonkasi @OncoAlert @cityofhopeoc @DrawImpacts Thank you for your guidance!

Crossed 160 publications📝today. ✍🏽Building upon #immunotherapy💉, novel clinical trials, and #liquidBiopsies🩸 for patients with colorectal cancer and other malignancies. Latest article with⭐️@mariaf_teix 🔗: @OncoAlert sciencedirect.com/science/articl… @cityofhopeoc #CRCSM #cancer

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1/n Setidegrasib the first-in-human, first-in-class, KRAS G12D-targeted protein degrader #TPD Our KRAS G12D degrader study is now published in the New England Journal of Medicine @NEJM nejm.org/doi/full/10.10… A new way to target KRAS G12D - one of the most common oncogenic drivers across cancers.

Here is the dilemma(s)— 1- do we have the right staging to avoid an “overkill” 2- do we really need a double hit with neoadjuvant IO followed by surgery ? Is NOM viable ? Perhaps but then follow up more tricky vs rectal — Role of MRD? Not yet 3- Chemo makes zero sense so do we go with surgery then IO only ? For how long ? Bottom line all options have issues and limitations — bottomline - if surgery first then IO x 6 months may be enough - if preop , carefully consider NOM - more data coming in next 1-2 years that will help with more clarity

🚀 KRAS: From “Undruggable” to the Hottest Target in Oncology 🔥🧬 KRAS is the most mutated oncogene in cancer - yet for decades it was “undruggable.” 2025 marks a turning point. A brand-new Signal Transduction & Targeted Therapy review lays out the ENTIRE evolution: • Why KRAS drives PDAC, CRC, NSCLC • Why G12C inhibitors work but only partly • Why resistance is inevitable • What the next wave of KRAS therapies looks like 🔑 Key takeaways: 🧩 KRAS mutations = ~30% of all cancers – PDAC: 80–90% – CRC: ~40% – NSCLC: ~20% (G12C dominant) 🧬 Approved “OFF-state” inhibitors: •Sotorasib •Adagrasib ➡️ ORR ~30–40%, PFS ~6 months. ➡️ Resistance? Guaranteed. 🔥 Major resistance mechanisms: – Secondary KRAS mutations (Y96D/S, G13D, A59…) – RTK pathway upregulation – EMT & squamous transformation – KRAS amplification – KEAP1/STK11/TP53 co-mutation biology 💡 The future = multi-modal KRAS targeting: – Pan-RAS inhibitors – G12D inhibitors (MRTX1133-like) – SOS1/SHP2 inhibitors combos – KRAS degraders (PROTACs) – KRAS vaccines & cell therapies – RNA & antisense therapeutics 🧠 The review beautifully shows KRAS as a signaling “master switch” with MAPK, PI3K, Ral, RAC1, Hippo/YAP-TAZ crosstalk explaining why single-agent inhibition fails. 🎯 Bottom line: KRAS is no longer undruggable - it’s just very hard to drug. The next breakthroughs will come from combos + pan-KRAS + epigenetic modulation + TME targeting. 🔖 Save this - it’s THE 2025 roadmap for KRAS-targeted therapy. 📖 Full paper cited below. #OncoTwitter #MedTwitter #LCSM #GIOnc #TargetedTherapy @myESMO @OncoAlert @ESMO_Open

Out today 🆕🩸 Our paper on #ctDNA liquid biopsy in patients on immunotherapy is live. Big thanks to @pashtoonkasi for the sharp feedback and thoughtful guidance. sciencedirect.com/science/articl…

🆕 📰 Published today👇🏽 “Utility of Circulating Tumor DNA-Based Liquid Biopsies in Patients with #Cancer Receiving Immunotherapy.” From our ⭐️ fellow @mariaf_teix 🩸🧬 #ctDNA and focus🔬on immunotherapy! @OncoAlert 🔗🆓for 50 days: authors.elsevier.com/a/1mZiT3lyy0y1…

⭐️🚨 🧬 Hot off the press 👉🏼A new chapter in cancer biology’s foundational text 👉🏼 🚨Hanahan’s “Hallmarks of Cancer-Then and Now, and Beyond” drops in @CellCellPress updating the framework that has shaped 25 years of oncology research, precision oncology & clinical trials The roadmap evolves. Required reading @OncoAlert 📌 cell.com/cell/fulltext/…

For adults with metastatic HER2-positive #BiliaryTractCancer, zanidatamab led to longer overall survival and reduced pain, supporting its role as a precision therapy option. ja.ma/4qH0JGx

Good timing with #GI26. 🗞️ Published today📝 @NatureComms Tucatinib➕Trastuzumab Mountaineer 🏔️ regimen HER2 ➕/RAS➖Metastatic colorectal cancer #CRCSM 🔗 nature.com/articles/s4146… 🔑 findings are that responses seen regardless of the method of testing 🔬🆚🧬🆚🩸 @OncoAlert

🧬 Straight from the press @JCOPO_ASCO Our case report of a platinum-refractory germ cell tumor with a somatic BRIP1 mutation and clinical response to olaparib. Grateful to collaborate with @arafflemd and colleagues ascopubs.org/doi/10.1200/PO…

Jaw-dropping ctDNA data in rectal cancer thanks to the GALAXY study (the gift that keeps on giving)🤯🧬. This prospective cohort from Japan looked at stage II–III rectal cancer treated with upfront surgery, no neoadjuvant therapy. It gives us one of the cleanest looks yet at postoperative ctDNA and who actually benefits from adjuvant chemo. 🩸 In the MRD window (2–10 weeks postop): • 14% ctDNA positive → very high recurrence risk (HR ~10) • 86% ctDNA negative → excellent outcomes with or without adjuvant therapy 💊 The key finding: Among ctDNA-negative patients, adjuvant chemotherapy did not show a statistically significant DFS benefit (HR 0.59, p = 0.21), 2 year DFS 86.1% vs 84.2%. The direction favors treatment, but the study didn't demonstrate benefit with very wide confidence intervals due to low numbers of ctDNA + patients (35). The HR implies improvement, but the curves overlap... In contrast, ctDNA-positive patients clearly benefited from adjuvant chemo (HR 0.28). 📈 Serial testing mattered. Patients who remained ctDNA negative did extremely well, while those who converted to positive had a sharp rise in recurrence risk. Takeaway: This strongly questions the value of adjuvant chemotherapy in ctDNA negative rectal patients after upfront surgery irrespective of stage. Looking forward to discussing at #GI26 (and why ctDNA still isn't in NCCN CRC guidelines). @OncoAlert @TheGutOncLab

This was a really useful and DETAILED review in @NatureRevCancer on the impact of concomitant medications on treatment outcomes in patients with cancer receiving immune checkpoint inhibitors (everything from antibiotics to analgesics to supplements) nature.com/articles/s4156…

Truly brutal trial design