Intratumoral heterogeneity

Intratumoral heterogeneity has become the main obstacle in treatment of malignant diseases. Although it has been known for decades, that several morphologically different sub-populations of tumor cells do exist within an individual malignant tumor, the interest in this issue has been limited for a long time. Now-a-days, the interest in this field is raising again with the emergence of need for a more detailed analysis of tumor cell characteristics. It is essential to integrate and extend our knowledge of intratumoral heterogeneity and to sufficiently elucidate this fact because intratumoral heterogeneity is considered one of the main reasons for drug resistance and development of progressive metastases. New light has been shed on the significance of discovering new methods for determining intratumoral heterogeneity. These should assist to presume cancer progression including invasion, metastasis, drug resistance, disease relapse and to administer the most adequate treatment. Although no doubt exists that intratumoral heterogeneity is evident in several, if not most malignant tumors, its origin has not been confirmed, and still remains to be discussed. So far, two theories have been proposed that try to explain the development of intratumoral heterogeneity: the idea of ​​‘cancer stem cells’ and the idea of ongoing cancer cell mutations that implement different cell clones. Both theories are discussed as mutually restricted hypotheses in the literature; however, they play an essential role in explaining the occurrence of tumor cell heterogeneity