PXD052693

PXD052693 is an original dataset announced via ProteomeXchange.

Title	Development of next-generation retinoid pathway immunotherapeutics through targeting tumor ALDH1a3
Description	Aldehyde dehydrogenase (ALDH1) activity has long been established as a pro-tumorigenic feature of many cancers, yet the identification of specific isoforms that are enriched in cancer, the mechanism of action of this isoform(s), and viable therapeutic strategies to target this pathway have long remained absent. Whereas one of the well-established functions of the ALDH1a family is the conversion of retinaldehyde into retinoic acid to activate nuclear retinoid signaling, the retinoid pathway is paradoxically hypothesized as a cell-intrinsic tumor suppressor pathway. Here we resolve this long-standing conflict by showing that while ALDH1a3 is broadly overexpressed across diverse cancer types, ALDH1a3 expressing tumor cells often lose the sensitivity to retinoid signaling. Instead, all-trans retinoic acid produced by ALDH1a3 acts in a paracrine fashion to suppress anti-tumor immunity and promote tumor growth. We further used structure-based high throughput screening to develop a series of first-in-class, therapeutically viable antagonists of ALDH1a3 with potent anti-tumor immunotherapeutic activity, an excellent pharmacological profile and no evidence of toxicity. Findings of this study resolve prior contradictions in the retinoid pathway through the development of highly specific and potent ALDH1a3 inhibitors.
HostingRepository	PRIDE
AnnounceDate	2025-08-27
AnnouncementXML	Submission_2025-08-26_19:36:23.070.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yibin Kang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Ultra

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-29 19:54:33	ID requested
⏵ 1	2025-08-26 19:36:23	announced

Dataset with its publication pending

submitter keyword: Human cancer, ALDH inhibitors, cancer immunotherapy, retinoid antagonist

Yibin Kang
contact affiliation	Department of Molecular Biology; Kang Lab; Princeton University, Princeton, NJ, USA
contact email	ykang@princeton.edu
lab head
Yibin Kang
contact affiliation	Princeton Uninversity
contact email	ykang@princeton.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD052693
     1. Label: PRIDE project
     2. Name: Development of next-generation retinoid pathway immunotherapeutics through targeting tumor ALDH1a3