# CARE: A Molecular-Guided Foundation Model with Adaptive Region Modeling for Whole Slide Image Analysis

arXiv: https://arxiv.org/abs/2602.21637 · HTML: https://mlsanity.com/paper/2602.21637/

## Key facts

- Cited by 6 papers in the map (data through 14 Oct 2026).
- Builds on 28 of its 54 references that are in the map.
- First posted on arXiv 25 Feb 2026.

## Builds on (most cited first, 28 of 28)

- [Learning Transferable Visual Models From Natural Language Supervision](https://mlsanity.com/paper/2103.00020/) (2021)
- [DINOv3](https://mlsanity.com/paper/2508.10104/) (2025)
- [CoCa: Contrastive Captioners are Image-Text Foundation Models](https://mlsanity.com/paper/2205.01917/) (2022)
- [Attention-based Deep Multiple Instance Learning](https://mlsanity.com/paper/1802.04712/) (2018)
- [iBOT: Image BERT Pre-Training with Online Tokenizer](https://mlsanity.com/paper/2111.07832/) (2021)
- [Data Efficient and Weakly Supervised Computational Pathology on Whole Slide Images](https://mlsanity.com/paper/2004.09666/) (2020)
- [BiomedCLIP: a multimodal biomedical foundation model pretrained from fifteen million scientific image-text pairs](https://mlsanity.com/paper/2303.00915/) (2023)
- [Dual-stream Multiple Instance Learning Network for Whole Slide Image Classification with Self-supervised Contrastive Learning](https://mlsanity.com/paper/2011.08939/) (2020)
- [Scaling Vision Transformers to Gigapixel Images via Hierarchical Self-Supervised Learning](https://mlsanity.com/paper/2206.02647/) (2022)
- [DTFD-MIL: Double-Tier Feature Distillation Multiple Instance Learning for Histopathology Whole Slide Image Classification](https://mlsanity.com/paper/2203.12081/) (2022)
- [Whole Slide Images based Cancer Survival Prediction using Attention Guided Deep Multiple Instance Learning Networks](https://mlsanity.com/paper/2009.11169/) (2020)
- [Multimodal Whole Slide Foundation Model for Pathology](https://mlsanity.com/paper/2411.19666/) (2024)
- [Artificial Intelligence for Digital and Computational Pathology](https://mlsanity.com/paper/2401.06148/) (2023)
- [Modeling Dense Multimodal Interactions Between Biological Pathways and Histology for Survival Prediction](https://mlsanity.com/paper/2304.06819/) (2023)
- [PRISM: A Multi-Modal Generative Foundation Model for Slide-Level Histopathology](https://mlsanity.com/paper/2405.10254/) (2024)
- [Feature Re-Embedding: Towards Foundation Model-Level Performance in Computational Pathology](https://mlsanity.com/paper/2402.17228/) (2024)
- [Transcriptomics-guided Slide Representation Learning in Computational Pathology](https://mlsanity.com/paper/2405.11618/) (2024)
- [Pathologist-level classification of histologic patterns on resected lung adenocarcinoma slides with deep neural networks](https://mlsanity.com/paper/1901.11489/) (2019)
- [Predicting Axillary Lymph Node Metastasis in Early Breast Cancer Using Deep Learning on Primary Tumor Biopsy Slides](https://mlsanity.com/paper/2112.02222/) (2021)
- [Do Multiple Instance Learning Models Transfer?](https://mlsanity.com/paper/2506.09022/) (2025)
- [ViLa-MIL: Dual-scale Vision-Language Multiple Instance Learning for Whole Slide Image Classification](https://mlsanity.com/paper/2502.08391/) (2025)
- [Development and Evaluation of a Deep Neural Network for Histologic Classification of Renal Cell Carcinoma on Biopsy and Surgical Resection Slides](https://mlsanity.com/paper/2010.16380/) (2020)
- [Scalable Generation of Spatial Transcriptomics from Histology Images via Whole-Slide Flow Matching](https://mlsanity.com/paper/2506.05361/) (2025)
- [Frozen Feature Augmentation for Few-Shot Image Classification](https://mlsanity.com/paper/2403.10519/) (2024)
- [SurGen: 1020 H&E-stained Whole Slide Images With Survival and Genetic Markers](https://mlsanity.com/paper/2502.04946/) (2025)
- [MiCo: Multiple Instance Learning with Context-Aware Clustering for Whole Slide Image Analysis](https://mlsanity.com/paper/2506.18028/) (2025)
- [Towards Hierarchical Regional Transformer-based Multiple Instance Learning](https://mlsanity.com/paper/2308.12634/) (2023)
- [High-Resolution Spatial Transcriptomics from Histology Images using HisToSGE](https://mlsanity.com/paper/2407.20518/) (2024)

## Built on by (most cited first, 6 of 6)

- [Thinking in Scales: Accelerating Gigapixel Pathology Image Analysis via Adaptive Continuous Reasoning](https://mlsanity.com/paper/2605.19491/) (2026)
- [AGE-MIL: Anchor-Guided Evidence Learning for Patient-Level Prediction](https://mlsanity.com/paper/2606.12126/) (2026)
- [Pretraining Multiple Instance Learning Networks with Multi-Teacher Distillation from Pathology Slide Foundation Models](https://mlsanity.com/paper/2607.14703/) (2026)
- [From Patches to Evidence Balls: Class-Conditioned Evidence Retrieval for Few-Shot Whole Slide Image Classification](https://mlsanity.com/paper/2608.01104/) (2026)
- [Can Protein-Derived Knowledge Improve Pathology Foundation Models?](https://mlsanity.com/paper/2609.33178/) (2026)
- [Modeling Whole-Slide Images as Dynamic Tumor Microenvironment Fields](https://mlsanity.com/paper/2609.34451/) (2026)

## Abstract (arXiv)

Foundation models have recently achieved impressive success in computational pathology, demonstrating strong generalization across diverse histopathology tasks. However, existing models overlook the heterogeneous and non-uniform organization of pathological regions of interest (ROIs) because they rely on natural image backbones not tailored for tissue morphology. Consequently, they often fail to capture the coherent tissue architecture beyond isolated patches, limiting interpretability and clinical relevance. To address these challenges, we present Cross-modal Adaptive Region Encoder (CARE), a foundation model for pathology that automatically partitions WSIs into several morphologically relevant regions. Specifically, CARE employs a two-stage pretraining strategy: (1) a self-supervised unimodal pretraining stage that learns morphological representations from 34,277 whole-slide images (WSIs) without segmentation annotations, and (2) a cross-modal alignment stage that leverages RNA and protein profiles to refine the construction and representation of adaptive regions. This molecular guidance enables CARE to identify biologically relevant patterns and generate irregular yet coherent tissue regions, selecting the most representative area as ROI. CARE supports a broad range of pathology-related tasks, using either the ROI feature or the slide-level feature obtained by aggregating adaptive regions. Based on only one-tenth of the pretraining data typically used by mainstream foundation models, CARE achieves superior average performance across 33 downstream benchmarks, including morphological classification, molecular prediction, and survival analysis, and outperforms other foundation model baselines overall.