Deciphering the tubulin code: roles and mechanisms of microtubule post-translational modifications in gastrointestinal tumors: a narrative review

Introduction

Microtubules (MTs) are an essential component of the cytoskeleton and participate in key cellular processes such as the establishment of cell polarity, migration, and mitosis (1). MTs are hollow tubular polymers assembled from α/β-tubulin heterodimers and exhibit “dynamic instability,” enabling cells to rapidly adapt to environmental stimuli and morphological remodeling (2). Beyond their dynamic behavior, microtubule functions are tightly regulated by a diverse set of post-translational modifications (PTMs), which occur either on the C-terminal tails of tubulin or at specific residues, including α-tubulin Lys40, and encompass acetylation, detyrosination/tyrosination, polyglutamylation, polyglycylation, and methylation (3). PTMs can alter microtubule stability and mechanical properties and modulate interactions with microtubule-associated proteins (MAPs) and motor proteins, thereby giving rise to the “tubulin code”. An increasing body of evidence suggests that dysregulation of microtubule PTMs and their regulatory axes is closely associated with the initiation and progression of multiple diseases, particularly cancer (4). Recent evidence indicates that microtubule PTMs play important roles in several cancer-related processes, including mitosis, cell migration and invasion, angiogenesis, and mechanotransduction. They may also contribute to remodeling of the tumor microenvironment. Moreover, multiple regulatory enzymes, such as αTAT1, HDAC6, TTL, and VASH1/2, are aberrantly expressed in gastrointestinal cancers and have been associated with tumor progression and prognosis. In this review, we schematically summarize the major microtubule PTMs, their modification sites and regulatory enzymes, and the associated mechanisms in gastrointestinal tumors (Figure 1), and further synthesize the evidence across three dimensions: clinical associations, molecular mechanisms, and potential therapeutic strategies. We present this article in accordance with the Narrative Review reporting checklist (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-1-0099/rc).

Figure 1 Schematic illustration of major microtubule PTMs, their regulatory enzymes, and associated mechanisms in gastrointestinal tumors. PTM types are shown together with representative writer and eraser enzymes and their reported associations with tumor behavior. Am, polyamination/amines; CCA, cholangiocarcinoma; CCP, cytosolic carboxypeptidase; CRC, colorectal cancer; GC, gastric cancer; HCC, hepatocellular carcinoma; HDAC6, histone deacetylase 6; PC, pancreatic cancer; PTMs, post-translational modifications; TCPs, tubulin carboxypeptidases; TTL, tubulin tyrosine ligase; TTLLs, tubulin tyrosine ligase-like enzymes.

Methods

This narrative review was conducted to summarize the current evidence on microtubule PTMs in gastrointestinal tumors. Literature retrieval was primarily performed in PubMed, EMBASE, Web of Science, and Google Scholar. The initial literature search was conducted on January 25, 2026, and was updated on March 23, 2026 to include more recently published studies. The search strategy combined controlled vocabulary terms (including MeSH terms when applicable) and free-text terms related to microtubules, tubulin post-translational modifications, and gastrointestinal malignancies. Reference lists of relevant articles were also manually screened to identify additional eligible studies.

Eligible literature included peer-reviewed original articles, relevant review articles, and representative translational studies focusing on the clinical associations, molecular mechanisms, regulatory enzymes, or therapeutic implications of microtubule PTMs in gastrointestinal tumors. Non-English publications, conference abstracts without sufficient data, duplicate records, and studies not directly related to tubulin PTMs in gastrointestinal tumors were excluded. Literature screening and selection were performed independently by the authors, and any disagreements were resolved through discussion and consensus. The search strategy summary is presented in Table 1, and a detailed search strategy for one database is provided in Table S1.

Roles of microtubule PTMs in gastrointestinal tumors (clinical prognosis and functional implications)

Acetylation

Acetylation is one of the earliest identified microtubule PTMs, first discovered in Chlamydomonas flagella. It occurs predominantly at α-tubulin Lys40 (K40) and is catalyzed by αTAT1 (also known as MEC-17), whereas deacetylation is primarily mediated by HDAC6, with additional context-dependent regulation by sirtuin family members (5-7). Available evidence, predominantly from preclinical studies, suggests that microtubule acetylation contributes to migratory, invasive, and metastatic phenotypes in several gastrointestinal tumors.

In hepatocellular carcinoma, CAMSAP2 promotes metastasis-associated phenotypes by stabilizing non-centrosomal MTs and increasing α-tubulin acetylation (8). In colorectal cancer models, αTAT1 has been linked to activation of Wnt/β-catenin signaling and enhanced migration and invasion, while αTAT1 knockout in HCT116 cells reduces microtubule acetylation and suppresses proliferation and invasion (5). In cholangiocarcinoma, dysregulation of the HDAC6-associated deacetylation pathway, with possible context-specific involvement of SIRT1, has been reported to alter microtubule acetylation, promote cytoskeletal remodeling, and enhance invasiveness (9,10). Collectively, these findings support a role for dysregulated tubulin acetylation in promoting aggressive cellular behavior in gastrointestinal malignancies. Nevertheless, current evidence remains largely mechanistic and preclinical, and further clinical studies are needed to clarify its prognostic and therapeutic significance in gastrointestinal cancers.

Detyrosination and tyrosination

Detyrosination/tyrosination is a major form of C-terminal tubulin modification, occurring primarily at the terminal tyrosine residue of α-tubulin; detyrosination is mainly mediated by the VASH1/2-SVBP complex, whereas TTL re-ligates tyrosine to the α-tubulin C-terminus, establishing a dynamic and reversible balance (11-13). This balance influences cell polarity establishment and migratory capacity by regulating microtubule stability and dynamics.

Across multiple gastrointestinal tumors, VASH1/2 expression correlates with invasiveness and metastatic phenotypes. The VASH1/2-SVBP complex mediates tubulin detyrosination and regulates microtubule stability (14). In colorectal cancer models, LRP6 overexpression increases tubulin tyrosination and microtubule dynamics, thereby promoting invasion and metastasis (15). Overall, detyrosination is generally associated with enhanced microtubule stability and directed migration, whereas tyrosination is linked to increased microtubule dynamics. These modifications may influence metastatic behavior by regulating polarity establishment, leading-edge protrusion, and adhesion turnover.

Polyglutamylation and polyglycylation

Polyglutamylation is an important class of microtubule PTMs that occurs widely on the C-terminal tails of α/β-tubulin and is catalyzed by tubulin tyrosine ligase-like (TTLL) enzymes, which add glutamate side chains of varying lengths to tubulin tails to alter interactions with binding proteins and motor proteins and influence microtubule stability and intracellular transport, while CCP enzymes provide reversible regulation (16,17). TTLL4 is highly expressed in pancreatic ductal adenocarcinoma (PDAC); TTLL4 downregulation suppresses tumor cell proliferation, whereas overexpression promotes tumor growth by enhancing polyglutamylation activity, implicating TTLL4 as a potential oncogenic factor in PDAC (18). Polyglutamylation can also influence vesicular/endosomal transport by modulating the binding efficiency of motor proteins, including KIF5B, to MTs (19). Polyglycylation likewise occurs on the C-terminal tails of α/β-tubulin and is also mediated by TTLL enzymes (20); in colorectal cancer studies, reduced TTLL3 expression is associated with decreased polyglycylation and impaired primary cilium formation, and because primary cilia inhibit Wnt signaling, their loss may relieve Wnt pathway suppression, promote intestinal epithelial proliferation, and increase malignant transformation risk (21).

Other tubulin PTMs

Beyond acetylation, detyrosination/tyrosination, polyglutamylation, and polyglycylation, tubulins can also undergo other PTMs, including phosphorylation, polyamination, and methylation. Among these, phosphorylation has an established role in mitotic regulation. In particular, Cdk1-mediated phosphorylation of β-tubulin at Ser172 has been shown to impair tubulin incorporation into MTs and contribute to mitosis-associated microtubule reorganization (22). Functional studies further support the importance of this residue for proper microtubule dynamics and cell division (23). In addition to tubulin itself, Cdk1-dependent phosphorylation of microtubule-associated regulators also contributes to spindle assembly and mitotic microtubule organization. However, direct evidence regarding the relevance of tubulin phosphorylation in gastrointestinal tumors remains limited. Polyamination represents another less-explored tubulin PTM. Previous mechanistic studies have shown that transglutaminase-catalyzed polyamination can stabilize MTs, particularly in long-lived cellular structures, suggesting a potential role in maintaining microtubule integrity (24). Nevertheless, substantive tumor-specific evidence, especially in gastrointestinal malignancies, is still lacking; therefore, polyamination should currently be regarded as a potentially relevant but insufficiently characterized component of the tubulin code in cancer. Methylation has clearer potential relevance to tumor biology. In addition to being acetylated, α-tubulin Lys40 can also be methylated by SETD2, indicating that distinct PTMs may compete for the same residue and suggesting hierarchical regulation within the tubulin code (25). Mechanistic studies further indicate that SETD2-mediated α-tubulin methylation is important for mitotic progression, spindle organization, cytokinesis, and maintenance of genomic stability (25,26). SETD2 loss or mutation has also been reported in gastrointestinal cancers, particularly colorectal and gastric cancers, where it has been associated with genomic instability, aggressive tumor behavior, and potential therapeutic relevance. However, the direct clinical significance of tubulin methylation itself in these tumor types remains to be further defined. Overall, these observations suggest that less-studied tubulin PTMs and PTM crosstalk further broaden the functional complexity of the tubulin code; however, most current evidence remains mechanistic or preclinical, and further validation in gastrointestinal tumors is still needed.

Molecular mechanisms by which microtubule PTMs drive tumor initiation and progression

Migration and invasion

Multiple microtubule PTMs play pivotal roles in tumor cell migration and invasion. In hepatocellular carcinoma, upregulated CAMSAP2 enhances microtubule stability and increases α-tubulin acetylation, thereby promoting invasion- and metastasis-associated phenotypes (8). An acetylated/stabilized microtubule state is associated with the spatial distribution of GEF-H1 and the consequent activation of RhoA-ROCK signaling, which enhances cellular contractility and motility (27); meanwhile, acetylated MTs can heighten mechanosensitivity to matrix stiffness, promote YAP nuclear translocation, and amplify invasive phenotypes. Beyond signaling regulation, acetylation of α-tubulin at Lys40 promotes vesicular transport and the processive movement of motor proteins, such as kinesin and dynein, thereby potentially contributing to directional migration and the maintenance of cell polarity (28). In colorectal cancer, elevated GEF-H1 activates the RhoA-MLC2 pathway and markedly enhances migratory and invasive behaviors (29). Detyrosinated MTs can stabilize APC at the leading edge and promote polarity establishment, thereby supporting directional migration (30). In addition, polyglutamylation influences intracellular trafficking and migration by modulating motor-microtubule binding efficiency; for example, TTLL7-mediated polyglutamylation of β-tubulin can restrain excessive KIF5B binding and tune its long-range transport mode, thereby improving transport fidelity and maintaining trafficking homeostasis (19).

Mitosis and genome stability

Microtubule PTMs are likewise critical for mitosis and the maintenance of genome stability. Detyrosinated MTs enhance CENP-E-mediated chromosome movement and capture, helping to reduce chromosomal instability (31). Acetylated MTs are enriched in the spindle region and favor spindle structural homeostasis, thereby ensuring faithful mitotic progression (32). Moreover, SETD2 mediates trimethylation at α-tubulin K40 (TubK40me3) to promote spindle function and cytokinesis during G2/M; loss of SETD2 can cause chromosome misalignment, multipolar spindles, and cytokinesis failure, thereby increasing the risk of genomic instability (26). Notably, some PTM-associated enzymes, such as TTLL4, can modify non-tubulin substrates; for instance, TTLL4-mediated polyglutamylation of PELP1 can alter its interactions with chromatin and contribute to chromatin remodeling, suggesting that PTM enzymes may influence tumor progression through parallel “cytoskeleton-chromatin” pathways (18).

Angiogenesis

Microtubule acetylation and detyrosination participate in endothelial lumen formation and angiogenesis by enhancing microtubule stability and regulating cell polarity, potentially involving end-binding protein 1 (EB1), dynactin subunit 1 (p150Glued), and cytoplasmic linker associated protein 1 (CLASP1)-mediated microtubule assembly and polarity signaling as well as downstream pathways such as rapidly accelerated fibrosarcoma (Raf)-extracellular signal-regulated kinase (ERK) signaling (33). With respect to detyrosination control, both VASH1 and VASH2 can form complexes with SVBP to mediate microtubule detyrosination. VASH2 has been reported to promote neovascularization across multiple tumor models; however, it should be noted that most of this evidence is derived from non-gastrointestinal tumor types (34). Emerging data suggest a potential association between VASH2 and angiogenesis in gastrointestinal tumors, but direct mechanistic evidence remains limited. Collectively, these findings suggest that microtubule PTMs may contribute to tumor progression by reshaping the endothelial cytoskeleton and thereby altering tumor vascular phenotypes.

Tumor microenvironment

Microtubule PTMs may shape the tumor immune microenvironment by influencing intracellular trafficking and stress signaling. First, microtubule polyglutamylation can alter the binding and processive motility of motor proteins such as KIF5B, thereby affecting major histocompatibility complex (MHC)-dependent endosomal trafficking routes and antigen-presentation-related processes (19). Second, under metabolic or proteostasis stress, changes in microtubule acetylation correlate with the intensity of the unfolded protein response (UPR) and may regulate tumor-cell survival and invasiveness via pathways such as protein kinase RNA-like endoplasmic reticulum kinase (PERK) and activating transcription factor 6 (ATF6) (35). Third, beyond regulating microtubule deacetylation, HDAC6 can deacetylate the chaperone heat shock protein 90 (HSP90) to affect signal transducer and activator of transcription 3 (STAT3) stability and transcriptional activity, thereby upregulating immunosuppressive molecules such as vascular endothelial growth factor (VEGF), interleukin-10 (IL-10), and programmed death-ligand 1 (PD-L1) and promoting immune evasion (36-39). It should be noted that evidence for the “microtubule PTMs-immune microenvironment” axis varies across tumor types, and gastrointestinal cancers still require validation with additional tissue specimens and mechanistic experiments. Overall, microtubule PTMs may cooperatively shape the immune microenvironment through multiple steps—antigen presentation, stress adaptation, and immunosuppressive factor expression—thereby providing potential targets and a theoretical basis for combination immunotherapy.

Mechanotransduction

Microtubule acetylation plays an important role in cellular mechanotransduction. Focal adhesions can recruit αTAT1 and promote microtubule acetylation, thereby enhancing cellular sensing of matrix stiffness; meanwhile, microtubule state changes are linked to spatial regulation of GEF-H1/RhoA signaling, promoting actomyosin contraction and driving YAP nuclear translocation to cooperatively enhance adhesion and motility (27). Matrix stiffening can also increase microtubule polyglutamylation, enhance microtubule stability, and promote metastasis-associated phenotypes (40). Conversely, under low shear stress, reduced microtubule acetylation can increase microtubule dynamics, thereby promoting integrin β1 internalization and recycling; as a key step in mechanotransduction, integrin β1 endocytosis and recycling regulate focal-adhesion turnover, disassembly of adhesion structures, and polarity establishment, thereby markedly enhancing the directional migration capacity of tumor cells (41). Based on these advances, we summarize the major microtubule PTM types, regulatory enzymes, associated tumor types, and potential mechanisms (Table 2).

Strategies for targeting microtubule PTMs as anticancer therapies

Targeting enzymes that regulate microtubule PTMs

Microtubule PTMs are catalyzed by specialized enzymes that can be broadly categorized as “writers”, including αTAT1, TTLLs, and TTL, and “erasers” or “reversal enzymes”, including HDAC6, sirtuin family members, CCPs, and the VASH1/2-SVBP system. By remodeling the PTM landscape, these enzymes modulate microtubule stability and interactions with MAPs, thereby regulating tumor cell migration, proliferation, stress adaptation, and immune evasion, and thus represent potential therapeutic targets. HDAC6 is a key microtubule deacetylase and is frequently overexpressed in gastrointestinal malignancies, including colorectal cancer, where it is closely associated with tumor progression (42). In preclinical studies, HDAC6 inhibitors increase α-tubulin acetylation and modulate multiple survival- and stress-related pathways, thereby suppressing tumor growth. For example, WMJ-J-09 induces colorectal cancer cell death and activates liver kinase B1 (LKB1)-p38 mitogen-activated protein kinase (MAPK)-p53 signaling (43). In addition, mutant p53 can promote tumor growth by upregulating HDAC6, thereby enhancing tumor cell adaptation to endoplasmic reticulum stress and altering DNA damage responses (44). A novel selective HDAC6 inhibitor, 18d with an IC₅₀ of 1.3 nM, increases α-tubulin acetylation and modulates molecules including B-cell lymphoma 2 (Bcl-2), extracellular signal-regulated kinase 1/2 (ERK1/2), and PD-L1, exhibiting both antitumor and immunomodulatory effects (45). A growing body of work suggests that combining HDAC6 inhibitors with chemotherapeutic agents can yield synergistic sensitization and may enhance responses to PD-1/PD-L1 antibody-based therapies (46). Beyond HDAC6, PTM-related enzymes, including αTAT1, the TTL family, the VASH-TTL system, and sirtuin family members, also show promise as druggable targets and may represent priorities for future anti-metastatic and combination-therapy studies (47).

Microtubule stabilization and depolymerization

Taxanes, such as paclitaxel, have been widely used to treat gastric, esophageal, and colorectal cancers, but therapeutic efficacy is frequently compromised by acquired drug resistance. Recently, the novel microtubule stabilizer SSE1917, which targets the taxane-binding site, has exhibited low 50% growth inhibition (GI50) values in colorectal cancer cell lines, including HCT116, and has demonstrated favorable efficacy with lower toxicity in colorectal cancer mouse models, supporting its further development as a candidate agent for optimizing microtubule-stabilizing therapy (48). In addition, photoactivatable microtubule-targeting agents (MTAs) enable spatially selective activation to achieve localized effects, with the potential to improve tumor-specific efficacy while reducing systemic toxicity (49). To address common taxane-resistance mechanisms, including P-gp-mediated efflux and βIII-tubulin isoform expression, novel microtubule depolymerizers such as PM534 target the colchicine-binding site of tubulin and retain antiproliferative activity in multidrug-resistant models, offering potential alternatives for patients with resistant disease (50). Beyond these canonical resistance mechanisms, emerging evidence suggests that altered tubulin PTM profiles may themselves modulate tumor-cell sensitivity to MTAs, thereby representing an additional layer of therapeutic resistance and potential intervention.

Role of tubulin PTMs in resistance to MTAs

Emerging evidence suggests that alterations in tubulin PTM patterns may influence the response of tumor cells to MTAs, particularly taxanes. Among these PTMs, acetylation and detyrosination have attracted increasing attention because both are frequently associated with more stable microtubule subsets and may thereby alter how cancer cells respond to microtubule-directed stress. However, current evidence remains predominantly preclinical, and direct validation in gastrointestinal tumors is still limited. With respect to acetylation, studies in non-gastrointestinal tumor models have shown that elevated α-tubulin acetylation can correlate with reduced paclitaxel responsiveness. In lung cancer models, paclitaxel-resistant cells exhibited increased tubulin acetylation, and experimental enhancement of acetylation through αTAT1 overexpression or pharmacologic HDAC6 inhibition attenuated paclitaxel-induced apoptosis, at least in part through stabilization of the anti-apoptotic protein Mcl-1 (51). These findings suggest that tubulin acetylation may, in some contexts, contribute to MTA resistance. Nevertheless, broader cross-cancer evidence indicates that acetylated α-tubulin may function more robustly as a predictive biomarker of taxane response than as a universally causal determinant, underscoring the context-dependent nature of this association (4). By contrast, detyrosination appears to have a more direct mechanistic relationship with taxane response in some experimental systems. Increased α-tubulin detyrosination has been shown to enhance taxol-induced cytotoxicity by suppressing the activity of the detyrosination-sensitive microtubule depolymerase MCAK, thereby aggravating mitotic defects and promoting cell death during mitosis and the subsequent interphase (52). This suggests that distinct PTMs may influence MTA responsiveness through different mechanisms and should not be interpreted uniformly as either sensitizing or resistance-promoting marks.

These observations also have potential therapeutic implications. Because HDAC6 is a major tubulin deacetylase and is frequently dysregulated in gastrointestinal cancers, HDAC6 inhibitors have attracted interest as combination agents. Available evidence in gastrointestinal cancer and broader oncology literature suggests that HDAC6-targeted strategies may modulate chemosensitivity and, in selected settings, enhance the antitumor activity of paclitaxel or other anticancer agents (47,53). However, given that increased tubulin acetylation has also been associated with reduced paclitaxel-induced apoptosis in some models, the role of HDAC6 inhibitors as chemosensitizers should be considered context-dependent rather than universal. Overall, PTM-guided modulation of MTA sensitivity represents a promising but still incompletely defined translational avenue, and further studies are needed to determine whether acetylation or detyrosination signatures can be used as predictive biomarkers or therapeutic stratification tools in gastrointestinal malignancies.

Targeting microtubule-binding proteins

CAMSAP2 is a microtubule minus-end-binding protein that contributes to the stabilization of non-centrosomal MTs and tumor cell migration. In hepatocellular carcinoma, CAMSAP2 cooperates with the microtubule plus-end protein EB1 to activate the Trio-Rac1-JNK-c-Jun signaling cascade and thereby promote migration and invasion. Rac1 inhibitors, such as NSC23766, which has been used primarily in mechanistic studies, may inhibit this pathway and reduce invasive capacity, suggesting that this axis may be amenable to therapeutic targeting. Moreover, in colorectal cancer, CAMSAP2 can enhance migratory and metastatic capacity by activating the JNK/c-Jun/MMP-1 pathway (54), further supporting its potential as an anti-metastatic therapeutic target. Notably, compared with the traditional research focus on plus-end tracking proteins (+TIPs), microtubule minus-end regulators and minus-end tracking proteins (−TIPs) and the non-centrosomal microtubule stabilization they mediate are increasingly being systematically recognized as an emerging anti-metastatic intervention layer (55).

Strengths and limitations

This review has several strengths. First, it provides a focused synthesis of microtubule PTMs in gastrointestinal tumors, a topic that has been less systematically summarized compared with the broader literature in cell biology and neurobiology. Second, the review integrates the available evidence across three complementary dimensions—clinical associations, molecular mechanisms, and potential therapeutic strategies—thereby linking PTM biology with tumor progression and translational relevance. Third, in addition to acetylation and detyrosination/tyrosination, this review also includes polyglutamylation/polyglycylation and methylation, highlighting the complexity of the tubulin code and the diverse regulatory enzymes involved, such as αTAT1, HDAC6, TTL, TTLLs, and VASH1/2.

However, several limitations should also be acknowledged. First, much of the currently available evidence is derived from mechanistic studies and preclinical models, whereas direct clinical validation in gastrointestinal malignancies remains limited. Second, gastrointestinal tumors represent a biologically heterogeneous group, and findings from hepatocellular carcinoma, gastric cancer, colorectal cancer, cholangiocarcinoma, and pancreatic cancer may not be directly generalizable across tumor types. Third, for some PTM categories, particularly polyamination and certain aspects of methylation, direct evidence in gastrointestinal tumors is still scarce. In addition, the causal relationships among different PTMs, their spatiotemporal dynamics, and their crosstalk networks remain incompletely understood. Therefore, further tumor-specific studies integrating tissue-based validation, functional experiments, and clinical correlation analyses are needed to strengthen the translational significance of microtubule PTMs in gastrointestinal cancers.

Conclusions

Microtubule PTMs, including acetylation, detyrosination/tyrosination, and polyglutamylation/polyglycylation, represent an important regulatory layer that governs cytoskeletal function. By altering microtubule stability, dynamics, and mechanical properties and remodeling interactions between MTs and motor and binding proteins, these PTMs contribute to key processes such as cell proliferation, migration and invasion, and mitosis. Current evidence indicates that microtubule PTMs play important roles in invasion and metastasis, chemotherapy resistance, angiogenesis, mechanotransduction, and microenvironmental remodeling in gastrointestinal cancers, and that key nodes, including HDAC6, VASH1/2, TTL, and TTLLs, may be druggable. However, most available evidence remains mechanistic or preclinical, and systematic evidence is still limited regarding causal relationships across tumor types and PTMs, the spatiotemporal dynamics of these modifications, and networks of PTM crosstalk. Future studies should integrate large clinical cohorts with more precise spatial and mechanistic approaches. For example, spatial transcriptomics may help map the distribution of PTM-regulating enzymes within the tumor microenvironment, while single-cell transcriptomic or multi-omic profiling may clarify tumor-cell heterogeneity in PTM-related pathways. In parallel, high-resolution imaging approaches such as cryo-electron tomography may help resolve PTM patterns on individual MTs in situ. Despite the growing biological and translational interest in microtubule PTMs, standardized criteria for applying PTM-based therapeutic strategies in gastrointestinal tumors have not yet been established. Future clinical implementation will likely depend on the identification and validation of robust biomarkers, including tumor-specific PTM signatures, expression patterns of PTM-regulating enzymes, and molecular features associated with therapeutic responsiveness. Integrating PTM profiling into patient stratification frameworks may help refine treatment selection and facilitate the development of biomarker-guided and combination therapeutic strategies targeting the tubulin code in gastrointestinal malignancies. However, further GI tumor-specific clinical and translational studies are still needed before these approaches can be applied in precision oncology practice.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-1-0099/rc

Peer Review File: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-1-0099/prf

Funding: This work was supported by the National Natural Science Foundation of China (No. 82470653), the Henan Clinical Medical Scientist Program (No. HNCMS202403), and the Henan Province Medical Science and Technology Research Project (Nos. SBGJ202503004 and SBGJ202503003).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-1-0099/coif). All authors report that this work was supported by the National Natural Science Foundation of China (No. 82470653), the Henan Key Science and Technology Research Program Joint Fund (No. 232301420056), and the Henan Clinical Medical Scientist Program (No. S20240183). The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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