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Overcoming the obstacles: a personalized approach to cancer therapy

Every cancer is different. This difference is caused by the specific genetic make-up of each individual and of each tumor, making every cancer patient unique.

Background:

The genetic information that determines the fate of the cells in our body is stored in DNA. In each cell, this information is transcribed from genes into messenger RNA molecules, which are further translated into proteins carrying out the essential cellular functions.

Cancer is a disease that is driven by molecular dysfunctions, due to alterations of the genome that have occurred in one initiating cell, affecting its behavior and leading to uncontrolled cell growth, which eventually will form a cancerous tissue. Cancer genome alterations are sometimes due to environmental factors, such as radiation, UV light, or exposure to chemicals. However, in most cases, the reason for cancer initiation is unknown.

Advances in Next Generation Sequencing (NGS) technologies offer new opportunities for cancer care based on molecular profiling. We are now able to identify the genome alterations associated with each individual tumor with high precision. These alterations might comprise mutations (single base changes in a DNA sequence), chromosomal rearrangements such as translocations (DNA breaks that might lead to aberrant chromosome and gene structures), chromosomal copy number alterations (loss or duplication of a chromosome), or more subtle changes affecting the expression of particular genes (e.g. also reflecting the epigenome). This knowledge opens up the possibility of specifically targeting those alterations found in individual tumors. A treatment that is guided by molecular profiling is called a “precision medicine approach”.

Precision medicine and personalized treatment

For the majority of cancers, diagnosis is primarily based on clinical and tumor pathology information. The accompanying treatment follows well-established standard protocols, supported by long-term clinical experience, large clinical trials, and takes into account additional information such as age, type of tumor and stage. However, only a fraction of cancer patients respond to standard therapies. The reasons for this are not always well understood, one explanation being that cancer is a heterogeneous disease. Different sub-groups with specific molecular alterations exist within a cancer type, and each group may not show the same benefit from standard therapies.The concept of “precision medicine” taking into consideration the “precise molecular tumor profile” is thus becoming increasingly relevant for cancer treatment, moving from the “one size fits all” standard therapy to a more personalized healthcare.

This personalized approach also open new possibilities for patients for whom no standard treatment option exists, such as patients with late stage disease, or for rare cancer types. Rare cancer types need particular attention, since they collectively represent at least one fourth of all cancers.

A general definition of precision medicine is given by the National Cancer Institute at the National Institutes of Health (USA): “A form of medicine that uses information about a person’s genes, proteins, and environment to prevent, diagnose, and treat disease. In cancer, precision medicine uses specific information about a person’s tumor to help diagnose, plan treatment, find out how well treatment is working, or make a prognosis. Examples of precision medicine include using targeted therapies to treat specific types of cancer cells”.

In this definition “specific information” may refer to very different types of data, starting from scanning for a single mutation in a gene, to establishing a complete molecular landscape of the tumor encompassing its whole genome together with its encoded RNA messenger molecules.

Most commonly, so-called gene panel sequencing is employed for detecting single mutations in a cancer sample. This method is very useful but it only tests for mutations in a limited number of genes (those present on the “panel”). A large number of cancers are due to alterations that can only be identified by more comprehensive NGS methods.

Comprehensive methods include Whole-Exome Sequencing (WES) for analyzing the coding regions of virtually all genes, Whole-Genome Sequencing (WGS) to scan the whole genome, and RNAseq for the quantitative detection of encoded messenger RNAs.

In-depth molecular investigation of tumors integrating these different data levels offers the best chance for personalizing cancer therapy.

Further reading on this topic: https://www.ncbi.nlm.nih.gov/pubmed/28595192

The unique personalized analysis offered by Alacris Theranostics:

Alacris Theranostics offers a Comprehensive Molecular Tumor Analysis (CMTA), generating a detailed molecular profile of the individual tumor. Our unique powerful NGS analysis pipelines, which integrate WES, WGS and RNAseq, deliver a concise report to the clinician containing different levels of molecular information.

In a number of cases, this analysis offers a rationale for a new treatment strategy. It also delivers very precise information on the tumor sub-type, and other clinically-relevant markers, such as known resistance markers.

After comprehensive molecular analysis and thorough data interpretation, the CMTA supplies the doctor with the necessary information to guide the choice of treatment for the patient.

At Alacris Theranostics, we are working hard on deepening our understanding of cancer’s molecular complexity. However, it is important to note that currently available targeted therapies are still limited; the molecular alterations identified by the CTMA do not always have a match with a targeted drug.

If you are a patient interested in our services, please talk to your doctor/oncologist. The CMTA can only be ordered through your clinician.

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