This table presents the predicted binding free energy (ΔG, kcal/mol) obtained from molecular docking simulations between five shortlisted IGs proteins and six commonly used CRC chemotherapies, including Irinotecan (IRN), oxaliplatin (OXA), 5-fluorouracil (5-FU), lonsurf (trifluridine-tipiracil) (FTD-TPI), capecitabine (CAP), and leucovorin (LEU). More negative ΔG values indicate stronger predicted binding affinity. Docking results were used to comparatively rank IGs for their feasibility as potential drug carrier scaffolds and do not imply pharmacological activity or therapeutic efficacy.
We would like to thank Mrs. J.S.Sakkthi Prabha for formatting and proofreading the manuscript.
Author contributions
RA: Conceptualization, Investigation, Methodology, Writing—original draft. VB, SK, JR, and RS: Writing—review & editing, Funding acquisition, Resources. All authors read and approved the submitted version.
Conflicts of interest
The authors declare that there are no conflicts of interest.
Ethical approval
The study was approved by the AVMC Institutional Human Ethics Committee (IHEC) under protocol No. AVMC-2021-04-14. The study was conducted in accordance with the principles of the Declaration of Helsinki (2024 revision).
Consent to participate
Written informed consent was obtained from all participants prior to sample collection.
Consent to publication
Not applicable.
Availability of data and materials
The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.
Funding
Seed funding support to conduct this research (VMRF/Research/Seed Money/30th April, 2021) was provided by VMRF. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.
References
Xi Y, Xu P. Global colorectal cancer burden in 2020 and projections to 2040.Transl Oncol. 2021;14:101174. [DOI] [PubMed] [PMC]
Kobritz M, Nofi CP, Egunsola A, Zimmern AS. Financial toxicity in early-onset colorectal cancer: A National Health Interview Survey study.Surgery. 2024;175:1278–84. [DOI] [PubMed]
Braun T, Rade M, Merz M, Klepzig H, Große F, Fandrei D, et al. Multiomic profiling of T cell lymphoma after therapy with anti-BCMA CAR T cells and GPRC5D-directed bispecific antibody.Nat Med. 2025;31:1145–53. [DOI] [PubMed]
Keeratichamroen S, Subhasitanont P, Chokchaichamnankit D, Weeraphan C, Saharat K, Sritana N, et al. Identification of potential cervical cancer serum biomarkers in Thai patients.Oncol Lett. 2020;19:3815–26. [DOI] [PubMed] [PMC]
ProtParam [Internet].Switzerland: SIB Swiss Institute of Bioinformatics; c2025 [cited 2025 Apr 12]. Available from: https://web.expasy.org/protparam
Liu Y, Yang X, Gan J, Chen S, Xiao ZX, Cao Y. CB-Dock2: improved protein-ligand blind docking by integrating cavity detection, docking and homologous template fitting.Nucleic Acids Res. 2022;50:W159–64. [DOI] [PubMed] [PMC]
Vita R, Blazeska N, Marrama D; IEDB Curation Team Members; Duesing S, Bennett J, Greenbaum J, De Almeida Mendes M, Mahita J, Wheeler DK, et al. The Immune Epitope Database (IEDB): 2024 update.Nucleic Acids Res. 2025;53:D436–43. [DOI] [PubMed] [PMC]
Kurcinski M, Badaczewska-Dawid A, Kolinski M, Kolinski A, Kmiecik S. Flexible docking of peptides to proteins using CABS-dock.Protein Sci. 2020;29:211–22. [DOI] [PubMed] [PMC]
Gautam A, Chaudhary K, Kumar R, Raghava GP. Computer-Aided Virtual Screening and Designing of Cell-Penetrating Peptides.Methods Mol Biol. 2015;1324:59–69. [DOI] [PubMed]
Zhuang Y, Wang H, Jiang D, Li Y, Feng L, Tian C, et al. Multi gene mutation signatures in colorectal cancer patients: predict for the diagnosis, pathological classification, staging and prognosis.BMC Cancer. 2021;21:380. [DOI] [PubMed] [PMC]
Meng M, Zhong K, Jiang T, Liu Z, Kwan HY, Su T. The current understanding on the impact of KRAS on colorectal cancer.Biomed Pharmacother. 2021;140:111717. [DOI] [PubMed]
Chang DZ, Kumar V, Ma Y, Li K, Kopetz S. Individualized therapies in colorectal cancer: KRAS as a marker for response to EGFR-targeted therapy.J Hematol Oncol. 2009;2:18. [DOI] [PubMed] [PMC]
Stefani C, Miricescu D, Stanescu-Spinu II, Nica RI, Greabu M, Totan AR, et al. Growth Factors, PI3K/AKT/mTOR and MAPK Signaling Pathways in Colorectal Cancer Pathogenesis: Where Are We Now?Int J Mol Sci. 2021;22:10260. [DOI] [PubMed] [PMC]
Tang D, Kroemer G, Kang R. Oncogenic KRAS blockade therapy: renewed enthusiasm and persistent challenges.Mol Cancer. 2021;20:128. [DOI] [PubMed] [PMC]
Zhu C, Guan X, Zhang X, Luan X, Song Z, Cheng X, et al. Targeting KRAS mutant cancers: from druggable therapy to drug resistance.Mol Cancer. 2022;21:159. [DOI] [PubMed] [PMC]
Lu Y, Yang Y, Zhu G, Zeng H, Fan Y, Guo F, et al. Emerging Pharmacotherapeutic Strategies to Overcome Undruggable Proteins in Cancer.Int J Biol Sci. 2023;19:3360–82. [DOI] [PubMed] [PMC]
Chiang ZC, Chiu YK, Lee CC, Hsu NS, Tsou YL, Chen HS, et al. Preparation and characterization of antibody-drug conjugates acting on HER2-positive cancer cells.PLoS One. 2020;15:e0239813. [DOI] [PubMed] [PMC]
Polli JR, Balthasar JP. Cell Penetrating Peptides Conjugated to Anti-Carcinoembryonic Antigen “Catch-and-Release” Monoclonal Antibodies Alter Plasma and Tissue Pharmacokinetics in Colorectal Cancer Xenograft Mice.Bioconjug Chem. 2022;33:1456–66. [DOI] [PubMed] [PMC]
Yu Z, Zhang X, Pei X, Cao W, Ye J, Wang J, et al. Antibody-siRNA conjugates (ARCs) using multifunctional peptide as a tumor enzyme cleavable linker mediated effective intracellular delivery of siRNA.Int J Pharm. 2021;606:120940. [DOI] [PubMed]
Jin Z, Piao L, Sun G, Lv C, Jing Y, Jin R. Dual functional nanoparticles efficiently across the blood-brain barrier to combat glioblastoma via simultaneously inhibit the PI3K pathway and NKG2A axis.J Drug Target. 2021;29:323–35. [DOI] [PubMed]
Su Z, Xiao D, Xie F, Liu L, Wang Y, Fan S, et al. Antibody-drug conjugates: Recent advances in linker chemistry.Acta Pharm Sin B. 2021;11:3889–907. [DOI] [PubMed] [PMC]
Guidotti G, Brambilla L, Rossi D. Cell-Penetrating Peptides: From Basic Research to Clinics.Trends Pharmacol Sci. 2017;38:406–24. [DOI] [PubMed]
Bousis D, Verras GI, Bouchagier K, Antzoulas A, Panagiotopoulos I, Katinioti A, et al. The role of deep learning in diagnosing colorectal cancer.Prz Gastroenterol. 2023;18:266–73. [DOI] [PubMed] [PMC]
