BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: cancer treatment

Chimeric Antigen Receptor T-Cell Therapy: Successful Research to Improve Cancer Treatments

Cancer is when abnormal cells divide without control and spread to other parts of the body through the bloodstream and lymph systems to cause illnesses. Immunotherapy is a type of treatment that utilizes a person’s immune system to battle diseases like cancer. Under the branch of immunotherapy, there is a specific therapy that has been recently improved upon.

Chimeric antigen receptor (CAR) T-cell therapy is a treatment that stimulates T-cells to fight cancer by editing them in the lab so they can be released into the body to find and destroy cancer cells. This treatment has been successful in treating certain types of hematologic malignancies but unsuccessful on solid tumors. Hematologic malignancies are cancers that begin in blood-forming tissues such as the bone marrow and in the immune system. Examples of cancers that can be treated with the CAR T-cell therapy include leukemia, lymphoma, and multiple myeloma.CAR T-Cell Therapy 

CAR stimulates macrophage phagocytosis function against tumor cells and its immunomodulation capacity. Scientists have already achieved success with this therapy in B cell leukemia/lymphoma but are still caught up on complications with solid tumors. The main challenge about solid tumors arise from its immunosuppressive tumor microenvironment. There is also a limited effect on infiltration into the dense extracellular matrix of the solid tumors.

In this type of therapy, the macrophages are the most important aspect of the success in treatment. Macrophages play a central role in the crosstalk between the adaptive and innate immune system. The immune system defends the body and marks pathogens and cancer cells for macrophages to fight and engulf. The researchers at Zhejiang University partnered with a researcher at the Fujian Medical University and The First Affiliated Hospital and Center for Stem Cell and Regenerative Medicine to study macrophage specific CARs and the development of EGFRvIII (epidermal growth factor receptor variant III) Targeting CAR-iMACs. The chimeric antigen receptors were further genetically engineered into induced pluripotent stem cell (iPSC) derived macrophages (iMACs) so that the CAR treatment was more effective toward solid tumors. The firefly luciferase gene (Ffluc) was discovered to promote the research through the bioluminescence signal response from tumor cells.

Macrophages were equipped with receptors called pattern recognition receptors (PRRs) through the discovery of the importance of bioluminescence cell signaling. The chimeric antigen receptor was then reprogrammed to contain Toll/IL-1R (TIR), a domain containing adapter inducing interferon β. The TIR-containing CAR is a novel engineered PRR that recognizes antigen associated molecular patterns and enables macrophages with antigen dependent polarization to be more pro-inflammatory to aid immune cell therapies in cancer.

Connection to AP Biology:

The chimeric antigen receptor T cell therapy has a great deal of connections to our AP Biology class.

Cancers:

CAR treats certain types of cancers, usually those in the blood-forming tissues. As we learned in AP Bio, cancers form when a cell does not properly divide and bypasses the checkpoints in the mitosis cycle. These abnormal cells don’t always become cancerous but they no longer follow the signals to stop dividing, causing masses that could one day become cancerous. 

Macrophages & Phagocytosis:

Macrophages and phagocytosis was something that we learned about in the first semester. Macrophages are specialized cells that are involved in pathogen detection so that phagocytosis can occur and destroy bacteria and other harmful substances.

Phagocytosis occurs when a cell engulfs solid things into the cell. We learned about phagocytosis along with pinocytosis and receptor-mediated endocytosis. In CAR therapy, phagocytosis occurs to engulf pathogens and cancer cells.

Bioluminescence:PanellusStipticusAug12 2009

In AP Bio, we did not directly learn about bioluminescence but we learned about cell communication and cell signaling. In bacteria, there is quorum sensing and it allows bacteria to share information about cell density and adjust gene expression. In bioluminescence bacteria, the power to produce light is controlled by quorum sensing. One bioluminescent bacteria cannot light up on its own, but when multiple bioluminescent bacteria gather together, quorum sensing signals for the “light” to shine once it senses enough of the bacteria together.

Pilatph8

Customizing Cancer?

Oncologists are moving toward a future in which cancer treatment is customizable and specific to each patient. This is achieved through genomic testing. Medical News Today: Pancreatic cancer splits into four types, says genome study

As genes differ from person to person, the information from genomic testing is unique to each. This speaks to what we’ve learned recently in bio class about how cellular mutations cause cancer. Changes to the DNA of a cell, specifically to genes that control the cell cycle, could result in oncogenes. But, I digress. The drawback of this type of treatment is that oncologists are met with so much information that it becomes not useful,  making the treatments less personal than they should be.

CHALLENGING GENETICS

The reason for this is due to the inability to identify which test will be most useful for each patient. When genetic data is obtained, what it means for the patient isn’t exactly clear. The example given in an article by Andrew Ip states that “several inhibitors of the enzyme anaplastic lymphoma kinase (ALK) have proven effective in treating lymphoma, non-small cell lung cancer, and neuroblastoma, while other findings suggest one of the inhibitors can treat pediatric oncology patients”. Although information was found from research specifically for ALK, it appears that much more is affected by these inhibitors making it less “personalized” than intended. 

Another reason as to why genomic testing is so difficult is accessibility. It can be difficult to get the treatments to patients due to health insurance limitations. In another instance, according to Andrew, “oncologists in community settings … had difficulty handling tumor samples, faced long turnaround times for laboratory tests, and had limited access to targeted therapies. To make it more difficult, next-generation sequencing results are often provided as a pdf, which cannot be digitally integrated with a patient’s electronic health records”. It appears altogether that oncologists are hindered by the lack of seamless integration of genomic testing into daily scenarios.

THERE IS HOPE

Although it appears that oncologists are overwhelmed, there is progress being made to support them. 

At the Hackensack Meridian Health John Theurer Cancer Center, where Andrew practices oncology, genomic testing was put into action. An ill patient had two separate biopsies done, and the findings of both contrasted each other greatly. One specified that the cancer identified was incurable, while the genomic sequencing depicted the cancer as curable. The patient was treated with chemotherapy and made quick improvement. 

The Genomic Testing Cooperative joined with Hackensack Meridian Health to implement an “in-house genomic profiling center”. As stated in Andrews article, the center “analyzes 434 genes for solid tumors, searching for DNA and RNA mutations and chromosomal structural abnormalities. For blood cancers, the service generates a 177 gene panel hematology profile”.

This isn’t all. A new database to which will aid oncologists in using the genomic results, cancer types, cancer medicines and patient outcomes is being built there as well.

FUTURE ADVANCES

In order to fully take advantage of genomic sequencing, companies are turning toward artificial intelligence. The goal is for AI to be able to use information from genomics, drug trials, patient demographics, and past scientific research to provide its own efficient course of action. This is called a clinical decision support system or CDS. IBM Watson was to be a CDS but did not suffice.

Until then oncologists take what Andrew describes as a “holistic approach to care”. This involves working with multidisciplinary teams made up of radiologists, pathologists, medical oncologists, radiation oncologists, and surgeons. Altogether they are known as molecular tumor boards. It’s fascinating to see just how much goes into making cancer care especially personalized to each patient.

A New Hope For Remission

Cancer is defined as a disease that is caused by cells dividing uncontrollably and spreading to nearby tissue. Cancer can start almost anywhere in the human body and it is made up by a build up of cells called a tumor. Cancer lives throughout recorded history just as it does today, an unsolved mystery. The earliest findings of tumors and cancer can be found in ancient Egyptian Mummies, and the first recordings were found in 3000 BC in Egypt. Although they didn’t refer to it as cancer, they described it as 8 cases of tumors that were surgically removed. The words, “there is no treatment,” were written in those early recordings. They couldn’t be more wrong! I’ll let it slide though because their technology was 5000 years behind ours. There are in fact many treatments in the world for cancer and there are new ones being discovered every day. While there may not be a cure for cancer, there are many treatments that show more and more signs of remission.

What Treatments Are Available?

The most common and well known treatment for cancer is Chemotherapy. Chemotherapy is a drug treatment that relies on the injection of chemicals to kill all of the fast growing cells in the human body. Chemotherapy is somewhat of a flexible treatment because it doesn’t have to be the primary treatment. Chemotherapy can be used without using other treatments, after using other treatments, and to prepare you for other treatments. While this may sound very appealing and hopeful, the success rate of Chemotherapy isn’t as high as we’d like it to be. The success rate varies, but it’s evident that as the severity of the cancer increases, the effectiveness of treatment decreases. Furthermore, the side effects of chemotherapy are not only excruciating, but scarring. As stated, the treatment attacks all of the fast growing cells, including hair, skin blood intestinal cells. This will cause hair loss, nausea, vomiting, diarrhea, loss of appetite, fatigue, easy bruising and fever.

Side Effects of Chemotherapy.png

There are other treatments for cancer that are not related to Chemotherapy, such as surgery, targeted therapies, and supportive care. Surgery is one of the biggest options for early stage cancers that are not blood cancers. Surgically removing the tumor from the body is the motive of this form of treatment. One must take into account the size, location and stage of the tumor in question. Targeted therapies (precision medicine) are tailored to specific patients. Through this therapy, scientists are able to find five or six gene processes that essentially turn a cancer “on or off.” While supportive care isn’t exactly considered medicine, forms of meditation and fitness are said to ease the effects of cancer and cancer treatment.

A New Hope

Through extensive research and testing, a new hope for remission has been discovered. Immunotherapy is a known, newer method of treating cancer that, instead of directly killing the cancer cells, boosts one’s immune system and natural defenses. This is a type of biological therapy because it uses substances made from living organisms as treatment. A recently discovered form of Immunotherapy called  CAR T-cell therapy has proven to show a lot of promise. T-cells are a type of white blood cell that kills cells infected with a pathogen. In this new therapy, doctors take blood from the patient and separate the T-cells from it. They then genetically change these cells so that they specifically attach to a protein on cancer cells. After expanding the number of T-cells, the doctors inject them back into the body. This treatment, however, is not without its side effects. As these T-cells cells multiply, they release cytokines into the blood, causing nausea, vomiting, fever, headaches, and diarrhea. How has CAR T-cell therapy been effective? An experiment was done in 2010 on two individuals with Chronic lymphocytic leukemia using CAR T-cell therapy. Just after this experiment, both patients saw complete remission in their cancer. And now ten years later, these two individuals show complete remission. Although more research needs to be done, CAR T-cell therapy proves to be an effective, long term treatment for cancer.

 

 

 

 

New Understanding in Telomerase Structure: Can It Lead to New Cancer Treatment Medications?

Telomerase. They know what it is. They know what it does. They know it is involved with the formation of malignant tumors. Yet for years, cancer researchers could not figure out a way to curb telomerase activity. Not until recently, when a group of researchers at the University of California, Santa Cruz discovered an important structural component of telomerase that could lead to the development of new and more efficient cancer treatment medications.

But first things first: what even is telomerase? To understand the role of telomerase, we must first understand what a telomere is. Analogous to the “plastic tips of shoelaces”, telomeres are located at the tips of chromosomes to keep the ends of DNA from “fraying”, consisting of the repetition of the same nitrogenous base sequence over and over again. In humans, this base sequence is TTAGGG.

Screen Shot 2015-10-05 at 7.44.26 PM(Source: https://en.wikipedia.org/wiki/Telomere#/media/File:Telomere.png)

The sequence can be up to 15,000 base pairs long; however, each time a cell divides, the telomeres get shorter and shorter until they become they become too small to divide again. That is when the telomerase comes in; it adds nucelotides to the telomere to prevent it from becoming senescent, or at least prolong the cell’s life span.

Sounds like a good thing, right? Not when the telomerase gets out of control and does not allow for cells to die, causing a huge growth of cells that eventually evolve into malignant tumors.

What makes it hard for scientists to combat excessive telomerase activity is due to the enzyme’s unique and complex structure. In addition to its sophisticated quaternary structure, telomerase also has an RNA template that allows the telomerase to make the DNA bases (TTAGGG) for the telomere.

Screen Shot 2015-10-05 at 10.24.26 PM

(Source: https://vi.wikipedia.org/wiki/Telomerase#/media/File:Telomerase_illustration.jpg)

Researchers at UC Santa Cruz determined the structure of the RNA binding domain of telomerase and how the template border is dependent on how the protein and RNA components interact with each other. Understanding this interaction can help scientists develop cancer medications that more specifically inhibit telomerase. This is the first major advancement in telomerase research since November of 2010 when biochemists at UCLA created an unprecedented 3D model of telomerase’s RNA structure.

While this discovery is a major step forward in cancer treatment research,  some experts have their reservations against finding methods of inhibiting telomerase altogether.

However, regardless of the controversy surrounding telomerase inhibition in cancer treatment, this discovery will be useful in coming up with tactics to prevent aging, and improve treatments in other medical fields, such as burns, bone marrow transplants, and heart disease.

What do you think? Leave a comment below!

 

 

Original Article

Fighting Cancer with Protein P53

Despite the amazing diagnostic technologies, pharmaceuticals, and procedures of modern medecine, cancer still takes the lives of more than half a million people in the US every year. Characterized by the unmediated reproduction and metastasis of tumorous cells, the various forms of the disease have proved difficult to slow and often nearly impossible to cure. Treating cancer usually requires rigorous chemotherapy or invasive surgery, each involving painful side-affects and long recovery periods.

Chemotherapy, while effective, indiscriminately attacks cells that divide quickly. Thus, the fast-dividing cells lining the mouth and intestine as well as the cells that cause hair to grow are also affected, causing an array of side affects. Scientists have been searching for a new way to fight cancer that would only target cancer cells while letting healthy cells function unhindered. A team at University of California, Irvine may have found that method in protein P53, mutated forms of which are implicated in “nearly 40 percent of diagnosed cases of cancer.

P53 is responsible for repairing damaged DNA and causing apoptosis, or programmed cell death, in cells that are damaged beyond repair. In a mutated form, P53 does not function properly, allowing cancerous cells that would normally be destroyed to proliferate. A therapy that reactivated mutated proteins could potentially surpress tumors without causing the nasty side affects of current drugs. Also, since P53 is present in so many cancer cases, a single treatment could be used against many different forms of the affliction. However, since P53 proteins “undulate constantly, much like a seaweed bed in the ocean,” sites where medicinal compounds could bind are difficult to locate.

The UCI team had to reach across disciplinal boundaries, enlisting computer scientists, molecular biologist and others to find a usable binding site. With the help of molecular dynamics, the group constructed a simulation of P53’s movements, eventually locating a transient site that could bind with stictic acid, one of forty-five small molecules they tried. Unfortunately, stictic acid is not a viable compound for pharmaceuticals, but the scientists at UCI think that other small molecules with similar characteristics will likely have similar effects and make effective treatments.

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