Overcoming chemoresistance in mucinous adenocarcinoma: the impact of tumor microenvironment and genetic alterations
Background: Mucinous adenocarcinoma (MAC) is a rare, aggressive subtype of adenocarcinoma, distinguished by excessive extracellular mucin production. This feature impairs drug penetration and contributes to poor chemotherapy response and chemoresistance. Genetic mutations (e.g., KRAS, BRAF, PI3K/AKT...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Creative Pharma Assent
2025-06-01
|
| Series: | Journal of Applied Pharmaceutical Research |
| Subjects: | |
| Online Access: | https://japtronline.com/index.php/joapr/article/view/1032 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850037478664175616 |
|---|---|
| author | Kaniga Pandi Binoy Varghese Cheriyan Vishali Ramesh Sowparnika Murugavel Jaya Surya Venkatesan |
| author_facet | Kaniga Pandi Binoy Varghese Cheriyan Vishali Ramesh Sowparnika Murugavel Jaya Surya Venkatesan |
| author_sort | Kaniga Pandi |
| collection | DOAJ |
| description | Background: Mucinous adenocarcinoma (MAC) is a rare, aggressive subtype of adenocarcinoma, distinguished by excessive extracellular mucin production. This feature impairs drug penetration and contributes to poor chemotherapy response and chemoresistance. Genetic mutations (e.g., KRAS, BRAF, PI3K/AKT), epithelial-to-mesenchymal transition (EMT), alterations in the tumor microenvironment, and mucin barriers contribute to this resistance. Objective: This narrative review aims to comprehensively summarize the molecular and microenvironmental mechanisms behind chemoresistance in MAC and highlight emerging therapeutic strategies to overcome it. Results: Chemoresistance in MAC arises from oncogenic signaling, immune evasion, hypoxia, and mucin-mediated drug exclusion. Promising approaches include mucolytic agents, small-molecule inhibitors, immune checkpoint inhibitors, RNA-based therapies, and nanoparticle-assisted drug delivery. Precision medicine, which utilizes genomic and transcriptomic profiling, is advancing individualized treatment; however, clinical translation remains limited. Conclusion: Resistance in MAC stems from both genetic and microenvironmental factors. Understanding these mechanisms is crucial for developing more effective, personalized therapies to improve patient outcomes. Future efforts should focus on validating novel therapies through clinical trials, discovering predictive biomarkers, and exploring tumor heterogeneity with multi-omics technologies. Integrating targeted therapies with advanced delivery systems may offer significant advances in treating chemoresistant MAC. |
| format | Article |
| id | doaj-art-1427dcbe8ded451b9d1af9b05362e488 |
| institution | DOAJ |
| issn | 2348-0335 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Creative Pharma Assent |
| record_format | Article |
| series | Journal of Applied Pharmaceutical Research |
| spelling | doaj-art-1427dcbe8ded451b9d1af9b05362e4882025-08-20T02:56:51ZengCreative Pharma AssentJournal of Applied Pharmaceutical Research2348-03352025-06-01133769310.69857/joapr.v13i3.10321033Overcoming chemoresistance in mucinous adenocarcinoma: the impact of tumor microenvironment and genetic alterationsKaniga Pandi0Binoy Varghese Cheriyan1Vishali Ramesh2Sowparnika Murugavel3Jaya Surya Venkatesan4Department of Pharmaceutical Chemistry, Saveetha College of Pharmacy, Saveetha Institute of Medical and Technical Sciences, Chennai 602105, Tamil Nadu, IndiaDepartment of Pharmaceutical Chemistry, Saveetha College of Pharmacy, Saveetha Institute of Medical and Technical Sciences, Chennai 602105, Tamil Nadu, IndiaDepartment of Pharmaceutical Chemistry, Saveetha College of Pharmacy, Saveetha Institute of Medical and Technical Sciences, Chennai 602105, Tamil Nadu, IndiaDepartment of Pharmaceutical Chemistry, Saveetha College of Pharmacy, Saveetha Institute of Medical and Technical Sciences, Chennai 602105, Tamil Nadu, IndiaDepartment of Pharmaceutical Chemistry, Saveetha College of Pharmacy, Saveetha Institute of Medical and Technical Sciences, Chennai 602105, Tamil Nadu, IndiaBackground: Mucinous adenocarcinoma (MAC) is a rare, aggressive subtype of adenocarcinoma, distinguished by excessive extracellular mucin production. This feature impairs drug penetration and contributes to poor chemotherapy response and chemoresistance. Genetic mutations (e.g., KRAS, BRAF, PI3K/AKT), epithelial-to-mesenchymal transition (EMT), alterations in the tumor microenvironment, and mucin barriers contribute to this resistance. Objective: This narrative review aims to comprehensively summarize the molecular and microenvironmental mechanisms behind chemoresistance in MAC and highlight emerging therapeutic strategies to overcome it. Results: Chemoresistance in MAC arises from oncogenic signaling, immune evasion, hypoxia, and mucin-mediated drug exclusion. Promising approaches include mucolytic agents, small-molecule inhibitors, immune checkpoint inhibitors, RNA-based therapies, and nanoparticle-assisted drug delivery. Precision medicine, which utilizes genomic and transcriptomic profiling, is advancing individualized treatment; however, clinical translation remains limited. Conclusion: Resistance in MAC stems from both genetic and microenvironmental factors. Understanding these mechanisms is crucial for developing more effective, personalized therapies to improve patient outcomes. Future efforts should focus on validating novel therapies through clinical trials, discovering predictive biomarkers, and exploring tumor heterogeneity with multi-omics technologies. Integrating targeted therapies with advanced delivery systems may offer significant advances in treating chemoresistant MAC.https://japtronline.com/index.php/joapr/article/view/1032mucinous adenocarcinomachemoresistancetargeted therapytumor microenvironmentcancer stem cellsnanomedicine |
| spellingShingle | Kaniga Pandi Binoy Varghese Cheriyan Vishali Ramesh Sowparnika Murugavel Jaya Surya Venkatesan Overcoming chemoresistance in mucinous adenocarcinoma: the impact of tumor microenvironment and genetic alterations Journal of Applied Pharmaceutical Research mucinous adenocarcinoma chemoresistance targeted therapy tumor microenvironment cancer stem cells nanomedicine |
| title | Overcoming chemoresistance in mucinous adenocarcinoma: the impact of tumor microenvironment and genetic alterations |
| title_full | Overcoming chemoresistance in mucinous adenocarcinoma: the impact of tumor microenvironment and genetic alterations |
| title_fullStr | Overcoming chemoresistance in mucinous adenocarcinoma: the impact of tumor microenvironment and genetic alterations |
| title_full_unstemmed | Overcoming chemoresistance in mucinous adenocarcinoma: the impact of tumor microenvironment and genetic alterations |
| title_short | Overcoming chemoresistance in mucinous adenocarcinoma: the impact of tumor microenvironment and genetic alterations |
| title_sort | overcoming chemoresistance in mucinous adenocarcinoma the impact of tumor microenvironment and genetic alterations |
| topic | mucinous adenocarcinoma chemoresistance targeted therapy tumor microenvironment cancer stem cells nanomedicine |
| url | https://japtronline.com/index.php/joapr/article/view/1032 |
| work_keys_str_mv | AT kanigapandi overcomingchemoresistanceinmucinousadenocarcinomatheimpactoftumormicroenvironmentandgeneticalterations AT binoyvarghesecheriyan overcomingchemoresistanceinmucinousadenocarcinomatheimpactoftumormicroenvironmentandgeneticalterations AT vishaliramesh overcomingchemoresistanceinmucinousadenocarcinomatheimpactoftumormicroenvironmentandgeneticalterations AT sowparnikamurugavel overcomingchemoresistanceinmucinousadenocarcinomatheimpactoftumormicroenvironmentandgeneticalterations AT jayasuryavenkatesan overcomingchemoresistanceinmucinousadenocarcinomatheimpactoftumormicroenvironmentandgeneticalterations |