Kalluri Lab

In @embojournal from @KalluriLab & @mcandrews_kate @UTMDAnderson dissecting a novel mechanism of resistance to KRAS inhibitors: CDK8 remodels the tumor microenvironment and promotes resistance to KRASG12D inhibitors and daraxonrasib in #PancreaticCancer link.springer.com/article/10…

Are Hedgehog inhibitors making a comeback in #PancreaticCancer, this time with nuanced sequencing and combination regimen? Preprint of 1st line clinical trial in advanced PDAC, @DrMhidalgo @Perlmutter_CC (in collaboration with @Val_LeBleu @rkalluriMDPhD): medrxiv.org/content/10.64898…

A true “farm to table” effort at @MDAndersonNews funded by our #PancreaticCancer Moonshot. The 1st clinical trial of systemic exosomes targeting mutant KRAS in metastatic pancreatic cancer. Five years from @rkalluriMDPhD discovery to patients. No DLTs whatsoever to speak of.

ICYMI an interesting preprint from @KalluriLab @MDAndersonNews that addresses the pivotal question of targeting the correct immune checkpoint in combination with KRAS inhibition in #PancreaticCancer. Hint: it may not be aPD-1! And why blocking CTLA4 may have greater efficacy.

New preprint by @mcandrews_kate (previously @KalluriLab, now PI at @MDAndersonNews): CDK8 remodels the tumor microenvironment to resist the therapeutic efficacy of targeted KRASG12D inhibition in #PancreaticCancer In this preclinical study, Kate demonstrates that while acute inhibition of KRAS using MRTX1133 leads to infiltration by CD11c+ cells and T-cell infiltration, this window for "immune rejection" is narrow and longer term treatment with KRASi leads to reversal of the immune milieu to one of "immune evasion", orchestrated by tumor cell intrinsic CDK8, which enhances CXCL2-mediated TME remodeling. Targeting CDK8 with a pharmacological strategy, combined with anti-CTLA antibody, reverses this immune milieu back to one of rejection. The translational relevance is obvious since patients are typically on these KRASi longer than most published short term mouse studies. Understanding the immune dynamics over time is important.

Which are the highest cited original research publications in #PancreaticCancer over the past five years (from 2020 to 2024 end)? All metrics obtained from Google Scholar (caveat: GS tends to OVERESTIMATE citations but the trends are consistent overall). 🧵 Below:

A provocative keynote lecture by @rkalluriMDPhD @MDAndersonNews this morning at @NCICancerBio TBEL Consortium, titled "Cancer Without Disease", building on a concept Judah Folkman and Raghu wrote 20 years ago. nature.com/articles/427787a Love this perspective: "All cancer therapies are immunotherapies". Even targeted therapies like KRAS inhibition ultimately need the body's immune system to get across the last mile to eradicate tumors.