REVIEW article
Front. Oncol.
Sec. Molecular and Cellular Oncology
Deciphering Molecular Pathways Driving Cancer Invasion and Metastasis: Advances and Therapeutic Prospects
Provisionally accepted
Aziza Alshahrani1*
Arwa Al-subait2,3
Zahrah Asiri1
Sahar Saleh Alghamdi3Sarah Bin Saqyah3Tariq Alqahtani2,3
Njoud Altuwaijri4
Rawan Fitaihi4
Yahya F. Jamous5*- 1King Khalid University, Abha, Saudi Arabia
- 2King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- 3Health Sciences, King Saud Medical City, Riyadh, Saudi Arabia
- 4King Saud University, Riyadh, Saudi Arabia
- 5King Abdulaziz City for Science And Technology, Riyadh, Saudi Arabia
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Metastasis is the primary cause of cancer-related mortality worldwide. This narrative review integrates recent advances in the molecular circuits orchestrating metastatic progression, encompassing epithelial-to-mesenchymal transition (EMT), organotropism, extracellular matrix remodeling, angiogenesis, hypoxia-inducible signaling, tumor-cell migration modes, and tumor-immune interactions through expert-guided literature selection. We examined therapeutic innovations that disrupt these pathways, including EMT modulators, matrix metalloproteinase inhibitors, VEGF/VEGFR-targeted regimens, hypoxia-activated prodrugs, and next-generation immunotherapies such as immune-checkpoint blockade and chimeric antigen receptor T cells. Additionally, we discuss established nanotechnology-based delivery systems, advancing multi-omics integration, evolving single-cell analyses, and emerging CRISPR-Cas9 gene-editing applications as tools for improving metastasis detection, monitoring, and treatment. Despite this progress, translational obstacles persist, particularly regarding intratumoral heterogeneity, adaptive resistance, and limited preclinical model fidelity. Addressing these challenges requires biomarker-guided, multi-target therapeutic combinations, interdisciplinary collaboration, and globally inclusive clinical trials. This evidence underscores the need importance of integrated strategies that simultaneously target intrinsic tumor plasticity and microenvironmental support to transform metastatic cancer outcomes.
Keywords: cancer metastasis, mesenchymal-epithelial transition, Pre-metastatic niche, tumor heterogeneity, liquid biopsy, therapeutic resistance
Received: 13 Aug 2025; Accepted: 05 Nov 2025.
Copyright: © 2025 Alshahrani, Al-subait, Asiri, Alghamdi, Bin Saqyah, Alqahtani, Altuwaijri, Fitaihi and Jamous. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Aziza Alshahrani, ealshahrania@kku.edu.sa
Yahya F. Jamous, yjamous@kacst.edu.sa
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.