Drug resistance remains a major challenge in cancer treatment.

Microtubules, essential components of the cytoskeleton, are important targets of several anticancer drugs.

βIII-tubulin (TUBB3), originally identified as a neuronal-specific protein, is frequently overexpressed in various cancers and associated with aggressive tumour characteristics and poor therapeutic responses.

In a recent review published in Advanced Cancer Research, researchers provide a comprehensive overview of TUBB3 functions in malignant tumours, including its structural features, biological roles, regulatory mechanisms, interactions with other β-tubulin isoforms and contributions to drug resistance.

Although TUBB3 normally functions in neuronal microtubule organisation, cancer cells can exploit TUBB3-associated mechanisms to enhance survival under therapeutic stress.

Structural differences in TUBB3 influence microtubule dynamics and modify responses to microtubule-targeting agents.

In addition, genetic alterations, post-translational modifications and signalling networks involving PI3K/AKT, MAPK/ERK and EMT pathways contribute to TUBB3-mediated tumour progression and treatment resistance.

Key highlights include:

Distinct molecular characteristics: TUBB3 differs from other β-tubulin isoforms through unique structural features that regulate microtubule behaviour and cellular responses to anticancer therapies.

A context-dependent cancer biomarker: TUBB3 expression is associated with tumour aggressiveness and drug resistance in many cancers, but its clinical significance varies depending on tumour type, molecular background and treatment conditions.

A potential therapeutic opportunity: Targeting TUBB3-associated regulatory networks may provide new strategies to overcome treatment resistance.

However, selective intervention remains challenging due to β-tubulin family similarity, compensatory mechanisms and TUBB3’s physiological roles in normal tissues.

The review identifies TUBB3 as an important molecular link between cytoskeletal regulation, cancer signalling and therapeutic failure.

Future studies integrating multi-omics analysis, single-cell technologies and functional screening approaches may further clarify TUBB3-driven cancer vulnerabilities and support the development of more precise treatment strategies.

Source: ELSP