Emerging Frontiers in Colorectal Cancer Therapy: From Targeted Molecules to Immunomodulatory Breakthroughs and Cell-Based Approaches

Overview

Journal Dig Dis Sci

Date 2025 Jan 27

PMID 39869166

Authors

Nayeralsadat Fatemi

Seyedeh Nasim Mirbahari

Sascha Tierling

Fatemeh Sanjabi

Shabnam Shahrivari

Mandana AmeliMojarad

Melika AmeliMojarad

Meygol Mirzaei Rezaei

Parsa Nobaveh

Mehdi Totonchi

Ehsan Nazemalhosseini Mojarad

Affiliations

Soon will be listed here.

Abstract

Colorectal cancer (CRC) is ranked as the second leading cause of cancer-related deaths globally, necessitating urgent advancements in therapeutic approaches. The emergence of groundbreaking therapies, including chimeric antigen receptor-T (CAR-T) cell therapies, oncolytic viruses, and immune checkpoint inhibitors, marks a transformative era in oncology. These innovative modalities, tailored to individual genetic and molecular profiles, hold the promise of significantly enhancing patient outcomes. This comprehensive review explores the latest clinical trials and advancements, encompassing targeted molecular therapies, immunomodulatory agents, and cell-based therapies. By evaluating the strengths, limitations, and potential synergies of these approaches, this research aims to reshape the treatment landscape and improve clinical outcomes for CRC patients, offering new found hope for those who have exhausted conventional options. The culmination of this work is anticipated to pave the way for transformative clinical trials, ushering in a new era of personalized and effective CRC therapy.

References

Alluri P, Newman L . Basal-like and triple-negative breast cancers: searching for positives among many negatives. Surg Oncol Clin N Am. 2014; 23(3):567-77. PMC: 4304394. DOI: 10.1016/j.soc.2014.03.003. View

Gokulnath P, de Cristofaro T, Manipur I, Di Palma T, Soriano A, Guarracino M . Long Non-Coding RNA MAGI2-AS3 is a New Player with a Tumor Suppressive Role in High Grade Serous Ovarian Carcinoma. Cancers (Basel). 2019; 11(12). PMC: 6966615. DOI: 10.3390/cancers11122008. View

Sur V, Mazumdar A, Vimberg V, Stefani T, Androvic L, Kracikova L . Specific Inhibition of VanZ-Mediated Resistance to Lipoglycopeptide Antibiotics. Int J Mol Sci. 2022; 23(1). PMC: 8744867. DOI: 10.3390/ijms23010097. View

Fennell L, Kane A, Liu C, McKeone D, Fernando W, Su C . Mutation Marks an Aggressive Subtype of Mutant Colorectal Cancers. Cancers (Basel). 2020; 12(5). PMC: 7281581. DOI: 10.3390/cancers12051171. View

Tiwari A, Saraf S, Verma A, Panda P, Jain S . Novel targeting approaches and signaling pathways of colorectal cancer: An insight. World J Gastroenterol. 2018; 24(39):4428-4435. PMC: 6196338. DOI: 10.3748/wjg.v24.i39.4428. View

Hainsworth J, Meric-Bernstam F, Swanton C, Hurwitz H, Spigel D, Sweeney C . Targeted Therapy for Advanced Solid Tumors on the Basis of Molecular Profiles: Results From MyPathway, an Open-Label, Phase IIa Multiple Basket Study. J Clin Oncol. 2018; 36(6):536-542. DOI: 10.1200/JCO.2017.75.3780. View

Jin J, Kim D, Lee J, Han C, Min W, Park C . Immune suppression therapy in aplastic anemia: influencing factors on response and survival. Korean J Intern Med. 1995; 10(1):25-31. PMC: 4532026. DOI: 10.3904/kjim.1995.10.1.25. View

Kumar M, Thangavel C, Becker R, Sadayappan S . Monoclonal Antibody-Based Immunotherapy and Its Role in the Development of Cardiac Toxicity. Cancers (Basel). 2021; 13(1). PMC: 7795565. DOI: 10.3390/cancers13010086. View

Zhan L, Feng H, Liu H, Guo L, Chen C, Yao X . Immune Checkpoint Inhibitors-Related Thyroid Dysfunction: Epidemiology, Clinical Presentation, Possible Pathogenesis, and Management. Front Endocrinol (Lausanne). 2021; 12:649863. PMC: 8224170. DOI: 10.3389/fendo.2021.649863. View

10.

Ranieri G, Patruno R, Ruggieri E, Montemurro S, Valerio P, Ribatti D . Vascular endothelial growth factor (VEGF) as a target of bevacizumab in cancer: from the biology to the clinic. Curr Med Chem. 2006; 13(16):1845-57. DOI: 10.2174/092986706777585059. View

11.

Zhou J, Ji Q, Li Q . Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies. J Exp Clin Cancer Res. 2021; 40(1):328. PMC: 8522158. DOI: 10.1186/s13046-021-02130-2. View

12.

Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W . Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004; 350(23):2335-42. DOI: 10.1056/NEJMoa032691. View

13.

Rouyer M, Francois E, Sa Cunha A, Monnereau A, Bignon E, Jove J . Effectiveness of first-line cetuximab in wild-type RAS metastatic colorectal cancer according to tumour BRAF mutation status from the EREBUS cohort. Br J Clin Pharmacol. 2020; 87(3):1120-1128. DOI: 10.1111/bcp.14472. View

14.

Wei L, Lin Z, Xie S, Ruan D, Jiang W, Cui Y . Complete Response With Cetuximab-Based Treatment of Metastatic Colorectal Cancers: Two Case Reports and Literature Review. Front Oncol. 2022; 12:798515. PMC: 8888900. DOI: 10.3389/fonc.2022.798515. View

15.

Kopetz S, Guthrie K, Morris V, Lenz H, Magliocco A, Maru D . Randomized Trial of Irinotecan and Cetuximab With or Without Vemurafenib in BRAF-Mutant Metastatic Colorectal Cancer (SWOG S1406). J Clin Oncol. 2020; 39(4):285-294. PMC: 8462593. DOI: 10.1200/JCO.20.01994. View

16.

Watanabe J, Muro K, Shitara K, Yamazaki K, Shiozawa M, Ohori H . Panitumumab vs Bevacizumab Added to Standard First-line Chemotherapy and Overall Survival Among Patients With RAS Wild-type, Left-Sided Metastatic Colorectal Cancer: A Randomized Clinical Trial. JAMA. 2023; 329(15):1271-1282. PMC: 10114040. DOI: 10.1001/jama.2023.4428. View

17.

Shiravand Y, Khodadadi F, Kashani S, Hosseini-Fard S, Hosseini S, Sadeghirad H . Immune Checkpoint Inhibitors in Cancer Therapy. Curr Oncol. 2022; 29(5):3044-3060. PMC: 9139602. DOI: 10.3390/curroncol29050247. View

18.

He R, Zhao X, Liu J, Zhou Y, Zhang X, Cheng F . PD-1 and CTLA-4 inhibitors in combination vs. alone for the treatment of advanced melanoma: A systematic review and meta-analysis. Medicine (Baltimore). 2022; 101(41):e30561. PMC: 9575742. DOI: 10.1097/MD.0000000000030561. View

19.

Borelli B, Antoniotti C, Carullo M, Germani M, Conca V, Masi G . Immune-Checkpoint Inhibitors (ICIs) in Metastatic Colorectal Cancer (mCRC) Patients beyond Microsatellite Instability. Cancers (Basel). 2022; 14(20). PMC: 9599678. DOI: 10.3390/cancers14204974. View

20.

Awate S, Babiuk L, Mutwiri G . Mechanisms of action of adjuvants. Front Immunol. 2013; 4:114. PMC: 3655441. DOI: 10.3389/fimmu.2013.00114. View