Question

How did tumor heterogeneity develop and its importance for basic cancer research? The importance of TH for clinical oncology? Explain.

Answer 1

Cancer diseases are due to abnormal growth in cell with the potential to spread to other parts of the body. Cancer is a heterogenous disease but its heterogenity is not only in different patients but can be found in a single patient also. Tumor heterogenity means different tumour showing distinct morphological and phenotypic characters like cellular morphology, gene expression, motility, proliferation, and metastatic potential.

It can occured between tumours and within tumours. This heterogeneity of cancer cells can lead to significant challenges in effective treatment. Thus, it allows a better understanding of the disease. Moreover it gives an idea for creation of more advanced treatment strategies that incorporate knowledge of heterogeneity. Two models used to explain the heterogeneity of tumour cells--cancer stem cells and clonal evolution. A small subset of cells that are tumourigenic(ability to form tumors) are termed as cancer stem cells.This model shows heterogeneity observed between tumour cells is due to differences in the stem cells from where they originated. Evidence of the cancer stem cell model was shown in leukemias, glioblastoma, breast cancer and prostate cancer.This method has several limitations eg. the need to control immune response in the transplant animal, and the absence of required exogenous molecules or cofactors.The variation in stem cell is because of epigenetic changes, but it can also be from clonal evolution of the CSC population where advantageous genetic mutations can accumulate in CSCs and their progeny.

In clonal evolution tumours arise from a single mutated cell, and it can occur more mutations with its progress. This heterogeneity may arise subclones that will have an advantage over the others within the tumour environment, and these subclones are dominant in the tumour. This model gives more understanding of tumour growth, treatment failure, and tumour aggression that might occur during the natural process of tumour formation.

A patient’s treatment are truly based on the study of biopsy specimens of the primary tumor and it usually revolve around the oncogenic drivers. So, tumor architecture is made to understand the molecular changes within the tumor itself. Therefore, the biopsy of a primary tumor cannot provide of what could be in secondary deposits. Moreover, chemotherapy and radiotherapy made selection of resistant clones, induce new mutations and other genetic and chromosomal rearrangements. Thus, it provides genetic and non-genetic subclonal changes through which cancer can successfully overcome the barriers made by antitumoral therapy. In other way tumor heterogeneity helps in multiregional sequencing, analysis of autopsy samples, single-cell sequencing, and longitudinal analysis of liquid biopsy samples.

The genetic variants emerged after therapy came to the conclusion that resistance and response to therapy are determined by genetic variants. The advantage of tumor partioning in identifying the biologically relevant, agressive intratumoral subregions have significant importance for clinical oncology. It can determine the tumor regions for biopsy.