Asael Roichman
@asaelroichman.bsky.social
Postdoc in Josh Rabinowitz's lab at Princeton University, studying how diet affects cancer therapy
Thanks Caroline! 🙏
May 19, 2025 at 11:11 PM
Thanks Caroline! 🙏
20/ Thanks for reading this far! I hope you’ll check out the full story in the paper.
May 19, 2025 at 8:15 PM
20/ Thanks for reading this far! I hope you’ll check out the full story in the paper.
19/ Grateful to our funding sources, including @ludwigcancer.bsky.social, @su2c.bsky.social, and NJCCR.
May 19, 2025 at 8:15 PM
19/ Grateful to our funding sources, including @ludwigcancer.bsky.social, @su2c.bsky.social, and NJCCR.
18/ Thanks also to the anonymous reviewers, the @cellpress.bsky.social editorial team, and Deputy Editor @snarasimhan.bsky.social for their thoughtful input and support during the revision process.
May 19, 2025 at 8:15 PM
18/ Thanks also to the anonymous reviewers, the @cellpress.bsky.social editorial team, and Deputy Editor @snarasimhan.bsky.social for their thoughtful input and support during the revision process.
17/ This work would not have been possible without fantastic collaborations with the Donia lab (Sunghoon Hwang, Sophia Koval) the Kang lab (Qianying Zuo) and Jessie Guo’s lab!
May 19, 2025 at 8:15 PM
17/ This work would not have been possible without fantastic collaborations with the Donia lab (Sunghoon Hwang, Sophia Koval) the Kang lab (Qianying Zuo) and Jessie Guo’s lab!
16/ I'd like to thank Josh for his incredible mentorship throughout the project, and all the Rabinowitz lab members for their support—including: Wenyun Lu, Ricardo Cordova, Mike MacArthur, Jacob Boyer, @sarahmitchellphd.bsky.social, Craig Hunter, Rolf-Peter Ryseck, Jenna AbuSalim and more.
May 19, 2025 at 8:15 PM
16/ I'd like to thank Josh for his incredible mentorship throughout the project, and all the Rabinowitz lab members for their support—including: Wenyun Lu, Ricardo Cordova, Mike MacArthur, Jacob Boyer, @sarahmitchellphd.bsky.social, Craig Hunter, Rolf-Peter Ryseck, Jenna AbuSalim and more.
15/ Further research is needed to understand how these findings translate to humans. Nevertheless, they highlight the importance of considering diet and microbiota when evaluating drug exposure, preclinical efficacy, and inter-individual variability in therapeutic response.
May 19, 2025 at 8:15 PM
15/ Further research is needed to understand how these findings translate to humans. Nevertheless, they highlight the importance of considering diet and microbiota when evaluating drug exposure, preclinical efficacy, and inter-individual variability in therapeutic response.
14/ Using bioassay-guided fractionations we identified the key soy phytochemicals responsible: soyasaponins (SSA), which are transformed into soyasapogenols by the gut microbiome. Soyasapogenols activate liver CYP, leading to reduced PI3Ki exposure and loss of tumor control.
May 19, 2025 at 8:15 PM
14/ Using bioassay-guided fractionations we identified the key soy phytochemicals responsible: soyasaponins (SSA), which are transformed into soyasapogenols by the gut microbiome. Soyasapogenols activate liver CYP, leading to reduced PI3Ki exposure and loss of tumor control.
13/ We found it was soy, which is abundant in standard rodent chow! It wasn’t the soy protein, but rather the small molecules—phytochemicals—in soy that activated liver CYP in a microbiome-dependent manner.
May 19, 2025 at 8:15 PM
13/ We found it was soy, which is abundant in standard rodent chow! It wasn’t the soy protein, but rather the small molecules—phytochemicals—in soy that activated liver CYP in a microbiome-dependent manner.
12/ Next, we asked: what ingredient in chow is responsible for activating drug clearance, leading to the reduced efficacy in chow-fed mice?
May 19, 2025 at 8:15 PM
12/ Next, we asked: what ingredient in chow is responsible for activating drug clearance, leading to the reduced efficacy in chow-fed mice?
11/ The increased drug exposure wasn’t due to suppression of direct drug metabolism by the gut microbiota, but rather to reduced hepatic CYP450-mediated clearance.
May 19, 2025 at 8:15 PM
11/ The increased drug exposure wasn’t due to suppression of direct drug metabolism by the gut microbiota, but rather to reduced hepatic CYP450-mediated clearance.
10/ We then discovered that the effect was mediated by drug pharmacokinetics—drug exposure was higher in mice fed purified diets or treated with antibiotics.
May 19, 2025 at 8:15 PM
10/ We then discovered that the effect was mediated by drug pharmacokinetics—drug exposure was higher in mice fed purified diets or treated with antibiotics.
9/ After we were convinced the results were real and robust, we set out to investigate the mechanism. First, we found that antibiotics that ablate the microbiome also strongly enhance the anticancer activity of the drugs.
May 19, 2025 at 8:15 PM
9/ After we were convinced the results were real and robust, we set out to investigate the mechanism. First, we found that antibiotics that ablate the microbiome also strongly enhance the anticancer activity of the drugs.
8/ To test whether the control diet was the real driver, we ran the experiment shown in the first figure panels of the paper—directly comparing the two high-carb control diets (plus keto). The results were clear: the “secret sauce” boosting PI3Ki efficacy was switching to a purified diet!
May 19, 2025 at 8:15 PM
8/ To test whether the control diet was the real driver, we ran the experiment shown in the first figure panels of the paper—directly comparing the two high-carb control diets (plus keto). The results were clear: the “secret sauce” boosting PI3Ki efficacy was switching to a purified diet!
7/ But after more thought we realized the difference between our experiment and the previous—the key was the control diet used! While we used a control purified diet (which, like keto, is made of refined ingredients)—the previous study used a standard grain-based chow as control.
a man in a suit is sitting in a chair with the words `` control ! control ! control . ''
ALT: a man in a suit is sitting in a chair with the words `` control ! control ! control . ''
media.tenor.com
May 19, 2025 at 8:15 PM
7/ But after more thought we realized the difference between our experiment and the previous—the key was the control diet used! While we used a control purified diet (which, like keto, is made of refined ingredients)—the previous study used a standard grain-based chow as control.
6/ At this point, I remember coming to the lab complaining that I got these strange results and that my experiment had probably failed :/
May 19, 2025 at 8:15 PM
6/ At this point, I remember coming to the lab complaining that I got these strange results and that my experiment had probably failed :/
5/ We tested how varying protein levels in ketogenic and high-carb diets affect the anticancer efficacy of PI3Ki in mice. As expected, the drugs worked well on the keto diet. But surprisingly, PI3Ki showed similarly strong efficacy on the high-carb control diet too!
a close up of a man with his mouth open .
ALT: a close up of a man with his mouth open .
media.tenor.com
May 19, 2025 at 8:15 PM
5/ We tested how varying protein levels in ketogenic and high-carb diets affect the anticancer efficacy of PI3Ki in mice. As expected, the drugs worked well on the keto diet. But surprisingly, PI3Ki showed similarly strong efficacy on the high-carb control diet too!
4/ As sometimes happens in science, this project began with a serendipitous result I observed at the end of my first postdoctoral year ->
a south park cartoon shows a man and a woman talking about the odds
ALT: a south park cartoon shows a man and a woman talking about the odds
media.tenor.com
May 19, 2025 at 8:15 PM
4/ As sometimes happens in science, this project began with a serendipitous result I observed at the end of my first postdoctoral year ->
3/ This project builds on the beautiful work by the Cantley lab, which showed that low-carbohydrate ketogenic diet dramatically enhances PI3K inhibitor (PI3Ki) efficacy in murine cancer models. www.nature.com/articles/s41...
Suppression of insulin feedback enhances the efficacy of PI3K inhibitors - Nature
Glucose–insulin feedback can reactivate PI3K in tumours treated with PI3K inhibitors, reducing therapeutic efficacy, but this effect can be reduced by using drugs or diet to suppress the insulin respo...
www.nature.com
May 19, 2025 at 8:15 PM
3/ This project builds on the beautiful work by the Cantley lab, which showed that low-carbohydrate ketogenic diet dramatically enhances PI3K inhibitor (PI3Ki) efficacy in murine cancer models. www.nature.com/articles/s41...
Link to the paper: www.cell.com/cell/fulltex...
Microbiome metabolism of dietary phytochemicals controls the anticancer activity of PI3K inhibitors
Diet can impact anticancer drug activity. A classic example in rodents is a ketogenic
diet enhancing PI3K inhibitor activity. Here, we show that phytochemicals and their
microbiome derivatives, rather...
www.cell.com
May 19, 2025 at 8:15 PM
Link to the paper: www.cell.com/cell/fulltex...