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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.

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 in turn translated into the proteins that carry out essential functions within our cells.

Cancer is driven by the accumulation of molecular dysfunctions. A multi-step process that begins with alterations within the genome of one initiating cell, leading to uncontrolled cell growth and division and eventually the formation of cancerous tissue. These 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 genomic alterations associated with each individual tumor with high precision. The nature of these alterations is varied, and can include 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 pathology examinations. The accompanying treatment follows well-established standard protocols, supported by long-term clinical experience and large clinical trials, and takes into account additional information such as the tumor type and stage as well as the patient’s age. However, only a fraction of patients with cancer responds to standard therapies. The reasons for this are not always well understood, but one explanation is that cancer is a heterogeneous disease. Even within the same cancer type, different sub-groups exist with specific molecular alterations, each one potentially reacting differently to standard therapies. The concept of ‘precision medicine’ taking the detailed molecular profile of a tumor into account is thus becoming increasingly relevant for cancer treatment, moving from the ‘one-size-fits-all’ standard therapy to a more personalized approach.

This personalized healthcare strategy also opens up new possibilities for patients for whom no standard treatment option exists, such as patients with late stage disease or for rare cancer types. Rare cancers are of particular concern as despite their ‘rare’ status they collectively represent at least one-quarter of all cancers.

According to the National Cancer Institute at the National Institutes of Health (USA), precision medicine is defined as, “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” refers to a range of data types with varying levels of detail, starting from a single mutation in a gene to the complete molecular landscape of a tumor, the latter 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. These 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.

An in-depth molecular investigation of tumors, integrating data on multiple 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:

Our Comprehensive Molecular Tumor Analysis (CMTA) service generates a detailed molecular profile of individual tumors.

We deploy our unique, powerful NGS analysis pipelines, integrating WES, WGS, and RNAseq, and conduct comprehensive molecular analyses and data interpretation. The findings are summarized and delivered to your doctor as a concise report containing different levels of molecular information. The report will provide precise information on the tumor sub-type, and other clinically-relevant markers, such as known resistance markers, and in a number of cases, will offer a rationale for a new treatment strategy.

The CMTA supplies your doctor with essential information that will help them decide on the best treatment strategy for you.

Here at Alacris Theranostics, we are working hard on deepening our understanding of cancer’s molecular complexity. It is important to note, however, that not all molecular alterations identified by the CTMA will find a match with a targeted drug – a drug that interferes with specific molecules involved in cancer – as options are still limited.

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

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