Thread by @sue_heavey

(1/13) Please RT: our first #tweetorial!

Here's a 🧵on our new paper which is also my 1st time being (joint) last author✍️

Congrats to all, especially superstar med student @LuszczakSabina!

#AcademicTwitter @AcademicChatter @OpenAcademics #womeninSTEM

nature.com/articles/s4159…

(2/13) In #prostatecancer cell lines & human tissue, co-targeting #PIM & #PI3K #kinases seems promising!

We reckon ~20% of prostate cancer patients could benefit from this approach in future & these tend to be the sicker patients.

Scroll for #science!

nature.com/articles/s4159…

(3/13) Fig1a:

From publicly available data we see that some patients overexpress either the #PIM pathway, the #PI3K pathway, or both. Each of these targets have inhibitors in development, that could theoretically be of benefit to any of these patient groups when combined 🤞

(4/13) Fig1b+c:

These patients who could hopefully benefit from this co-targeted approach also happen to tend to be sicker (higher Gleason, lower survival) 🏥

(5/13) Fig2:

At the RNA level in 3 #prostatecancer cell lines, inhibition of #PIM/ #PI3K lead to decreased expression of a range of downstream genes, & co-targeted inhibition of both pathways lead to decreased expression of a wider range of #genes, as you might expect!

(6/13) Fig3: At the phospho-protein level, we see similar trends, with the co-targeted approach yielding the most striking inhibition, particularly in the most aggressive cell line (C4-2B) - this was encouraging👍

(7/13) Fig4: All the inhibitors lead to dose-dependent reductions in proliferation in all cell lines, with the lowest IC50s coming from the triple kinase inhibitor #AUM302, in the nM range.

Nice drug! Thanks: @AumBiosciences @InflectionBio @CNIOStopCancer #drugdevelopment

(8/13) Fig5: In human #exvivo cultures, we see the same story, with improved inhibition of proliferation & induction of apoptosis when we co-target both pathways. Note the conc differences!

This fig is a taster of the work to be expanded on in my new lab #comingsoon #heaveylab

(9/13) limitations: the ex vivo work is only in a few patients, we may have been lucky & we can’t assume this would work so well for everyone – probably only around a fifth will respond like this. Or maybe more… only one way to find out!

(10/13) Next steps:@ProstateUK @MovemberUK have funded us to expand this cohort substantially & carry out detailed molecular work. Much of the collection & culture has already happened, with thanks to @UCLpathology @uclhrobotics

prostatecanceruk.org/research/resea… #fellowship #womeninSTEM

(11/13) Acknowledgements [part 1] for the work above!

Big thanks to the authors including these tweeters -follow them! @LuszczakSabina @HayleyWhitaker @kathygately1 @b3nsimp @hayleyjeanpye @linamacarmona @aimhaider @acesridhar @greglshaw @TheWhitakerlab
nature.com/articles/s4159…

(12/13) Acknowledgements [part 2] for the work above!

Many thanks for supporting this work:

Collab:@InflectionBio @AumBiosciences
Journal:@SciReports @SpringerNature
Funders:@ProstateUK @MovemberUK
Hosts:@UCLDivofSurgery @UCL @UCLpathology @uclhrobotics
nature.com/articles/s4159…

(13/13) Now we party? 🥳🙌🎊🎏

(⬇️please imagine them 2m apart 😷)

#publication #AcademicChatter #AcademicTwitter #WomeninSTEM #scicomm

nature.com/articles/s4159…