Lindonlight Collective ری ٹویٹ کیا
Lindonlight Collective
429 posts
Lindonlight Collective
@Lindonlight
To end pediatric brain cancer
Houston, TX شامل ہوئے Nisan 2024
39 فالونگ63 فالوورز
Lindonlight Collective ری ٹویٹ کیا
Lindonlight Collective ری ٹویٹ کیا
I did a PhD in the biology of p53 so, given this week's news, I can't resist sharing some facts about it
1. Cancers are under intense selective pressure to inactivate p53, and there are >1,000 ways to do it
2. Even one molecule of mutant p53 within the functional tetramer can poison the whole complex — many of the mutations are dominant-negative
3. Some p53 mutations not only disrupt its anti-tumor function, but add new pro-tumor functions (these are the 'gain-of-function' mutations)
We've known all of this for a long time, and it's amazing to see p53-reactivating therapies finally (slowly) having some success in the clinic
Samuel Hume@DrSamuelBHume
5 breakthroughs in medicine this week (I'm excited about this one) Read it here: breakingground.substack.com/p/can-we-final…
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Lindonlight Collective ری ٹویٹ کیا
देश की बेटियां स्वस्थ और समृद्ध हों, इसके लिए हम कोई कोर-कसर नहीं छोड़ रहे हैं। इसी दिशा में आज सुबह करीब 11:30 बजे राजस्थान के अजमेर में एचपीवी टीकाकरण के देशव्यापी अभियान का शुभारंभ करूंगा। इस पहल का उद्देश्य सर्वाइकल कैंसर की रोकथाम है। इस दौरान कई परियोजनाओं के शिलान्यास और उद्घाटन के साथ ही अपने युवा साथियों को नियुक्ति पत्र देने का भी सुअवसर मिलेगा।
pib.gov.in/PressReleasePa…
हिन्दी
Lindonlight Collective ری ٹویٹ کیا
📢📢Big day for HIF-2α inhibition — the Belzutifan era is expanding in RCC✅
🧬LITESPARK-011 (2L mRCC)
Belzutifan + lenvatinib vs cabozantinib
PFS HR 0.70
24-mo PFS: 35.6% vs 19.1%
Strong and clinically meaningful signal.
🧬LITESPARK-022 (adjuvant)
Belzutifan + pembrolizumab vs pembro
DFS HR 0.72
~7% absolute gain at 2 yrs
OS immature.
From metastatic to adjuvant —
HIF-2α inhibition is clearly entering prime time. @OncoAlert @OncoReporte @MedwatchKate @MedicalwatchHQ @weoncologists @Uromigos
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@morrisoi37 @grok - is this AI or real? If real, where and what plane?
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Lindonlight Collective ری ٹویٹ کیا
Lindonlight Collective ری ٹویٹ کیا
A brief history of p53-targeting cancer therapies
2003 — Gendicine, a p53 gene therapy, approved in China (but not elsewhere)
2012 — The first small molecule MDM2 inhibitor (RG7112, which works by preventing degradation of p53) enters trials, but did not progress to approval
2013 — Second-generation MDM2 inhibitor (Idasanutlin) reached phase 3, but failed and was dropped
2017 — A dual MDM2/MDMX inhibitor, ALRN-6924, enters trials; it has not since been approved
2020–2021 — A mutant p53 reactivator, Eprenetapopt, fails in phase 3
2023 — An MDM2 inhibitor, Milademetan, fails in phase 3
2024 — Promising phase 1 data for an MDM2 degrader
2026 — Rezatapopt phase 1 data: very promising early data, specific for the p53 Y220C mutation (present in 1% of all solid tumours)
NEJM@NEJM
Original Article: Phase 1 Study of Rezatapopt, a p53 Reactivator, in TP53 Y220C–Mutated Tumors (PYNNACLE study) https://nej.md/3OIQC5P Science behind the Study: Restoring Function to a Variant of p53 in Solid Tumors https://nej.md/3N0pQW8 #Oncology #Genetics
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Lindonlight Collective ری ٹویٹ کیا
Our work is now published in @Nature.
We introduce the Mouse Cancer Cell Line Atlas (MCCA) and reveal deterministic, tissue-specific rules of KRAS-driven cancer evolution.
Huge thanks to the entire team & collaborators.
nature.com/articles/s4158…
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Lindonlight Collective ری ٹویٹ کیا
Lindonlight Collective ری ٹویٹ کیا
Having two copies of APOE e2 is seriously like a genetic superpower. These people almost never get Alzheimer's, no matter how old they get.
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Lindonlight Collective ری ٹویٹ کیا
Real world intracranial efficacy of trastuzumab deruxtecan (T-DXd, HER2 ADC) in HER2 mutant NSCLC @JTOonline. Systemic RR 54.8%, PFS 7.2m, OS 18.3m across lines. As 1L, RR 72.2%, OS 22.1m. Intracranial RR 74.1% in 27 pts. ILD seen in 14% (4 fatal).
jto.org/article/S1556-…
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@JordynSilvs Hope it works out better than this NEJM phase I
nejm.org/doi/full/10.10…
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When New England Journal publishes a phase I trial...you know its something interesting
TP53 Y220C Reactivator: Rezatapopt
> 7 out of 15 evaluable patients with ovarian cancer had responses and prolonged ones at that (see below)
> The most common AEs: nausea, vomiting, anemia
> Serious AEs with this novel strategy included pneumonitis, pyrexia, ALT/AST elevation and AKI -> clearly a lot to learn
One interesting point was 4 patients underwent biopsies on progression and one of the 4 had two new TP53 variants – this is early data and hard to draw any conclusions but with any novel therapies have to make sure we aren’t breeding more resistant clones with our treatments – time will tell
#Gynonc @OncLive
Jordyn Silverstein, MD@JordynSilvs
To be able to target the un-targetable has been an emerging theme in cancer therapeutics and I’m proud of be a part of this field. Excited about this one- and the study is open at UCLA for TP53 Y220C mutated solid tumors
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@PTarantinoMD @chadinabhan The field’s mistaken belief that higher payload potency would translate to better clinical efficiency delayed progress by at least a decade
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ADCs have been around for 40 years. Why, then, did they reach the headlines only now? And how will their role evolve in oncology? A pleasure to join @chadinabhan on this broad discussion on All Things ADCs. Tune in 🎙️👇
chadi nabhan MD, MBA, FACP@chadinabhan
My #HealthcareUnfiltered podcast with @PTarantinoMD of @DFCI_BreastOnc is streaming on my @YouTube channel. Check it out, comment, and join the conversation. youtu.be/Xe10UHU_7Ss?si…
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@PTarantinoMD @chadinabhan Deruxtecan and its clones
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Lindonlight Collective ری ٹویٹ کیا
When a phase 1 trial is published in @NEJM, you can bet it will be impactful. Here, the p53 reactivator rezatapopt showed an ORR 20% among 77 pts with TP53 mutant (Y220C) advanced tumors. Are we getting closer to drug the most undruggable of all mutations? nejm.org/doi/full/10.10…
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Lindonlight Collective ری ٹویٹ کیا
Fast walkers have higher IQ & larger brains than slow walkers.
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@PTarantinoMD Only with payload diversity and if there is something like “the next Deruxtecan”
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Lindonlight Collective ری ٹویٹ کیا
Will ADCs replace chemotherapy? 🎯
chadi nabhan MD, MBA, FACP@chadinabhan
This Tuesday 2/24, I am joined by @PTarantinoMD of @DanaFarberNews @DFCI_BreastOnc who discusses "All things ADCs in Cancer." Wide range conversation that may generate more quetsions. Check out this clip, and mark your calendar this Tuesday morning for the full podcast.
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@PTarantinoMD @allisonoconn Mostly seen in trials in China
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@allisonoconn A recent breast oncology example is evERA, where you can see the full ladder 👇
Paolo Tarantino@PTarantinoMD
evERA: Doubling of PFS (5.4 to 10 months, HR 0.38, p<0.001), improvement in ORR and positive OS trend with giredestrant/eve vs SoC ET/eve in ESR1-mutant HR+ MBC. New fully oral SoC option for 2L treatment of pts with ESR1 mutations. Presented by @elmayermd @DFCI_BreastOnc #ESMO25
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Ah! Today I learned about “stair step” shape of survival curves on clinical trials!
Paolo Tarantino@PTarantinoMD
An example of how the PFS curves from LUNG-TIME-C01 differ from phase 3 trials, where scans are performed at set time points, producing the typical “stair step” shape. In LUNG-TIME-C01, the continuous shape of the KM curves resembles real-world studies Credit to Daniel Brickman
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