Detecting chemoresistance before treatment

This analysis explored whether class 3 β-tubulin levels are associated with chemoresistance in non-small cell lung cancer.

Non-small cell lung cancer often has no symptoms in the early stages, and therefore is often diagnosed at later stages. Despite treatment advances, the outlook for later-stage non-small cell lung cancer is still poor. One reason is chemoresistance, where the cells become resistant to the actions of certain chemicals which limits the benefits of chemotherapy. It is not clear what causes chemoresistance, but genetic factors are thought to play an important role. A method for identifying these factors in patients could decrease the use of chemotherapy (and its negative effects) in patients who are resistant.

Taxanes (such as docetaxel [Taxotere]) and vinorebines (such as vinblastine) are anti-tubulin agents (drugs that block tubulin, a protein found in cells) often used in non-small cell lung cancer. While previous studies have found that a high level of class 3 β-tubulin is associated with chemoresistance, other studies have not found this correlation.

The current analysis examined the connection between class 3 β-tubulin levels and chemoresistance to taxane and vinorebine chemotherapy agents.

This analysis included 28 studies and 2,401 patients. All studies examined the association between class 3 β-tubulin levels and response to taxane- or vinorebine-based chemotherapy. The analysis compared objective response rates (a measurable response such as tumor shrinkage), overall survival (time until death from any cause), and event-free survival (time from treatment until complication or symptom return).

Higher levels of class 3 β-tubulin were associated with a 75% increased chance of chemoresistance compared to lower levels. Patients with lower levels of class 3 β-tubulin were 76% more likely to show a response to taxane- or vinorebine-based chemotherapies than were patients with high levels.

Patients with high levels of class 3 β-tubulin had shorter overall survival times than patients with lower levels. Patients with high levels of class 3 β-tubulin were 47% more likely to have short event-free survival times than patients with low levels. 

This analysis concluded that high levels of class 3 β-tubulin are associated with lower objective response rates and shorter overall and event-free survival rates compared to low levels. The authors suggest high levels of class 3 β-tubulin could be a marker for chemoresistance in non-small cell lung cancer.