Lindonlight Collective

To end pediatric brain cancer

[Dr. Foxpaws Fauxpas @foxpaws_onco]

Continuing the #lung #cancer updates - 2025's practice changing updates in #lcsm
DELLPHI304 Tarlatamab
IMFORTE Lurbinectedin
MARIPOSA VS FLAURA2
TROPION Dato DxD
LUMINOSITY TelisoV
WUKONG Sunvozertinib
TRUST Taletrectinib
BEAMION Zongertinib
SOHO Sevabertinib

[Leah Pierson @leah_pierson]

omg this title, this paper

[Samuel Hume @DrSamuelBHume]

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

[Narendra Modi @narendramodi]

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 सर्वाइ���ल 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।

https://t.co/LHT7SdJrGc

[Uğur Özkerim @UOzkerim]

📢📢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

[Lindonlight Collective @Lindonlight]

@morrisoi37 @grok - is this AI or real? If real, where and what plane?

[Paolo Tarantino @PTarantinoMD]

Brief history of anti-p53 cancer treatments 👇

[Samuel Hume @DrSamuelBHume]

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)

[Markus Tschurtschenthaler @MarTschu]

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.
https://t.co/vjiwCcHnQl

[Gene Smith @GeneSmi96946389]

@RaskinSalmo @AlexTISYoung https://t.co/Wt7LL526Hm

[Gene Smith @GeneSmi96946389]

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.

[Stephen V Liu, MD @StephenVLiu]

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).

https://t.co/QMJ38D4Qf2

[Lindonlight Collective @Lindonlight]

@JordynSilvs Hope it works out better than this NEJM phase I

https://t.co/Bt1jA6xd8B

[Lindonlight Collective @Lindonlight]

@PTarantinoMD @chadinabhan The field’s mistaken belief that higher payload potency would translate to better clinical efficiency delayed progress by at least a decade

[Lindonlight Collective @Lindonlight]

@PTarantinoMD @chadinabhan Deruxtecan and its clones

[Paolo Tarantino @PTarantinoMD]

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? https://t.co/lpkvWiNNmu

[Path of Men @PathOfMen_]

Fast walkers have higher IQ & larger brains than slow walkers.

[Lindonlight Collective @Lindonlight]

@PTarantinoMD Only with payload diversity and if there is something like “the next Deruxtecan”

[Paolo Tarantino @PTarantinoMD]

Will ADCs replace chemotherapy? 🎯

[Lindonlight Collective @Lindonlight]

@PTarantinoMD @allisonoconn Mostly seen in trials in China