Cancer genome analysis provides breakthroughs in clinical understanding

The cancer genome sequencing project, which looked into the genetic make up of cancer cells, allowed the discovery of oncogenic mutations and led to valuable insights into the genomics of cancer.

The Cancer Genome Atlas (TCGA) is considered the most important scientific advance of this century. Genetic mutations responsible for cancer were cataloged to build a significant dataset to advance oncology and industry understanding of tumor development.

A genetic mutation is the permanent alteration of DNA and the respective change in functionality.

Unfortunately, despite all this exciting progress, the frequency of cancer is still on the rise.

How does tumor genome sequencing lead to personalized cancer treatment?

Since 2003, the sequencing of the entire human genome opened the way for researchers to study cancer genome.  The aim being to find driver mutations, which increase the mutation rate in the cell, that lead to a more rapid evolution of the tumor and metastases formation. 

Some of the mutations, known as passengers, do not drive progression to metastatic disease. Others, genetic drivers, are considered crucial to cancer cell survival and growth.

This information helps enable the possibility of personalized cancer therapy.

Chromosomal instability

Furthermore, chromosome instability is an indication of most solid tumors with aneuploidy being a direct result of chromosome instability. It is observed in about 90% of all solid tumors and may be a driver of cellular transformation .

Generally, hereditary cancers are defined by the presence of mutations in DNA repair genes, for instance BRCA1, BRCA2, MSH2 and MYH, which lead to genomic instability. This latter is present in all stages of cancer, from precancerous lesions; even before TP53 mutations are obtained, to advanced cancers.

In studies over the last 10 years, researchers have failed to show chromosomal instability in mouse model experiments as a driver in transformation. These experiments often needed an additional genetic alteration for tumorigenesis, tumor formulation, for instance the deletion of the p53, p21 or p19Arf tumor suppressor genes.

An experiment by Silk et al. showed aggravating the level of chromosome instability in mice model experiments increased cell death and reduced tumor growth. This result might be explained by the absence of cancer-causing entity in these animal models.

Including all types of DNA changes, many are left asking what makes genomic alterations viable in cancer cells?.

Targeted cancer therapies: Focus on the beginning

The fact is tumor DNA sequencing data shows that DNA mutations in cancer cells are multiple and heterogeneous. Adouda Adjiri suggested that future cancer research should focus on identifying the initial event responsible for the switch from normalcy to malignancy and what elements switch in this cell (normal versus malign) to the cause of cancer. This might result in cancer cure.


Weiterlesen Pharma-iq