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Tumor mutation burden (TMB): Why is it a key marker in cancer treatment?
In cancer treatment research laboratories, tumor mutation burden (TMB) has become an important indicator. This metric measures the number of non-inheritable mutations per million genome sequences, and its measurement capability has been improved through next-generation sequencing technologies. By observing the association between high TMB and DNA damage repair mutations, the researchers found that increases in these factors could be associated with the therapeutic effects of immune checkpoint inhibitors, thereby providing better clinical benefits to patients.
High TMB has been shown to be an important biomarker for predicting survival, regardless of cancer type, stage or grade.
The value of TMB as a biomarker
One of the survival mechanisms in tumors is to increase the expression of immune checkpoint molecules to suppress specific tumor T cells so that they cannot be recognized and eliminated. Immune checkpoint inhibitors (ICIs) have shown remarkable effectiveness in assisting the immune system to target tumor cells. Studies have shown that patients with high TMB tend to benefit more from ICIs therapy, which undoubtedly makes TMB an important predictive indicator.
Different levels of TMB are associated with patients' responses to immune checkpoint inhibitors, which makes us look forward to its subsequent clinical application.
Association of TMB with treatment response
Studies have shown that the higher the TMB, the higher the patient's response rate to immune checkpoint therapy. Data show that the ICIs response rate corresponding to a TMB level as high as 20 is 58%, while that below 20 is as low as 20%. As evidenced by multiple studies, TMB has clearly become an important consideration in the new generation of cancer treatment.
TMB variability across cancer typesTMB shows significant variability among different cancer types. Taking melanoma and non-small cell lung cancer as examples, these cancers generally have high TMB levels, while leukemia and certain pediatric tumors show lower TMB values. This variability is critical for developing cancer treatment strategies because different cancer types have different sensitivities to TMB.
Challenges of calculating TMBTumor heterogeneity and sample source (primary or metastatic) greatly affect the calculation of TMB and its subsequent therapeutic efficacy.
Currently, there are still differences in the calculation standards of TMB in different clinical and research environments. Overall, whole genome sequencing, whole exome sequencing, and panel-based approaches can all be used to calculate TMB, which raises important discussions about data consistency.
The accuracy of the data will directly affect whether we can accurately predict patients' response to immune checkpoint therapy and the stability of survival predictions.
Future Development Direction
Although the potential of TMB as a biomarker is widely recognized, challenges in its clinical application remain. Standardized test methods and an objective calculation framework are an important step in promoting its development. In addition, how to combine TMB with other biomarkers (such as PD-L1) to further improve the accuracy of treatment is also one of the current research focuses.
Among the many cancer treatment indicators, can TMB become the gold standard for cancer diagnosis and treatment in the future?
