Photo by National Cancer Institute on Unsplash
Breast cancer is the second most common cancer for women (after skin cancer) in the US. It actually isn't a single form of cancer -- nature generates it in a number of ways resulting in different types. A sample:
Invasive ductal carcinoma
Invasive lobular carcinoma
Inflammatory breast cancer
Paget's disease of the breast
Angiosarcoma of the breast
Phyllodes tumors
Ductal carcinoma in situ (DCIS)
Lobular carcinoma in situ (LCIS)
HER2 status
Triple-negative breast cancer
Metastatic breast cancer
We don't need to attack cancer directly anymore. Genes are the instruction set for life. When the genetic code develops an error, the wrong tissue (cancerous) can be created by the body. Editing the genetic code correctly means that the instructions for building new tissues will be delivered correctly, replacing the cancerous tissue with healthy new growth.
Before these new discoveries, because most combinations involved breast surgery, it was and still is a daunting prospect. Maybe not much longer:
Inspired with bacterial immune system, CRISPR/Cas9 came into existence as a revolutionizing powerful tool that facilitates correction, insertion, or deletion of genetic material both in vitro and in vivo systems. The discovery of this captivating bacterial immune defense mechanism resulted in an unprecedent revolutionary change in medical sciences
Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) and related CRISPR Associated (Cas#) are being used in editing therapy and are in human clinical trials that show promise of ridding bodies of cancer without surgery. The treatment involves drawing blood, sequencing the genetic code from the blood, editing the gene code with the CRISPR/Cas9 editing tools and then injecting the edited DNA back into the body. If the therapists correctly identify the damaged gene sequence and repair it, the repaired gene will generate new tissues free of the cancer malformation.
There are several trials involving breast cancer, but also trials of other forms of cancer involving CRISPR/Cas9.
Based on promising results of pre-clinical studies, the CRISPR/Cas9 system could also potentially be used clinically to target cancer-causing genes. At this time, eleven clinical trials are underway testing the effectiveness of CRISPR for cancer therapies.
There are many more pre-clinical studies getting ready for clinical trials. It's an exploding area of research.
Gene-editing technologies have provided a plethora of benefits to the life sciences. The clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9 (CRISPR/ Cas9) system is a versatile technology that provides the ability to add or remove DNA in the genome in a sequence-specific manner. Serious efforts are underway to improve the efficiency of CRISPR/Cas9 targeting and thus reduce off-target effects. Currently, various applications of CRISPR/Cas9 are used in cancer biology and oncology to perform robust site-specific gene editing, thereby becoming more useful for biological and clinical applications.
The reason research isn't evolving treatment faster is the concern for "off-target effects". Early CRISPR trials didn't work out as expected.
Jesse Gelsinger, an 18-year-old with a mild form of the genetic disease ornithine transcarbamylase (OTC) deficiency, participated in a clinical trial which delivered a non-mutated OTC gene to the liver through a hepatic artery injection of the recombinant adenoviral vector housing the therapeutic gene. Unfortunately, Jesse passed away 4 days after treatment. The adenovirus vector triggered a much stronger immune response in Jesse than it had in other patients, causing a chain of multiple organ failures that ultimately led to his death.
Jesse's death in 2003 and other off-target events have made the FDA understandably cautious. Fortunately, the addition of the CRISPR associated editing programs (CRISPR/Cas) have reduced the danger of off-target events by focusing on repairing genetic code by correcting specific known proteins and having them deliver changes to cells. Cas9 is by far the most used editor, but others are being used with more under development.
Editing genetic code has a short history. Starting with Francisco Mojica at the University of Alicante in Spain who developed CRISPR to edit genetic code in a bacterium (Mycobacterium tuberculosis) in 2000. Alexander Bolotin discovered cas9, a protein the body uses to fight disease in 2005.
In 2020:
Nobel Prize in Chemistry was awarded for the discovery of the CRISPR/Cas9 gene editing system, which has—for the first time—enabled scientists to make precise changes in the long stretches of DNA that make up the code of life for many organisms, including people. The prize was shared by Emmanuelle Charpentier, a microbiologist and director of the Berlin-based Max Planck Unit for the Science of Pathogens, and Jennifer A. Doudna, a professor and biochemist at the University of California, Berkeley.
For the award to be given for a breakthrough little over 5 years old is quite unusual. Usually, it is given as a "lifetime achievement" to some ready to retire researcher.
This transformative breakthrough is about to spawn dozens of companies ready to catapult into medical history and make investors rich. Many will fail, not because their solutions don't work, but because someone was faster or had better results.
Invest small amounts in many companies, rather than trying to pick winners. There are going to be a lot of surprises. There are going to be big winners.
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