BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: tumor

Prime Editing – a Revolutionary New CRISPR Variant

In the article I chose, the author discusses how researchers have discovered and applied a unique use of a new frontier in cancer research: CRISPR genome-editing. This technology offers countless possible insights into tumor mutations, as well as amazing implications for cancer biology and future treatment.

The article begins by mentioning how tumors harbor hundreds of mutations in hundreds of different genes, each having the ability to drastically change the trajectory of tumor development, progression, and plausible response to cancer-related treatment. It also states how finding and screening these genes accurately (at least prior to this advancement) has been extremely limited. That is until now! MIT researchers have begun utilizing prime editing, a variant of CRISPR, consequently unlocking a tool for deciphering the genetic intricacies of cancer.

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So far, the researchers demonstrated the capabilities of their technique by screening cells with over 1,000 different mutations and combinations of the tumor suppressor gene p53 – a lethal gene implicated in more than half of all cancer cases. Using prime editing, described as “faster and more efficient than any previous approach” by the author, enables precise editing of the genome, providing crucial information regarding the consequences of each mutation. The result: their findings were more than successful, revealing that certain p53 mutations, previously deemed benign, actually have both profound and adverse effects on cell and subsequently tumor growth. This discovery only further proves the importance of studying mutations with CRISPR as opposed to artificial systems,.

The potential of CRISPR extends far beyond p53. With its versatility and scalability, this technology could efficiently and effectively be applied to numerous other cancer-related genes and cases, offering understanding of tumor genetics and paving a new way for personalized cancer therapies that could operate with increases success.

In linking this back to our AP Biology curriculum, we can draw parallels to our recent study of genetics. We learned that even the smallest mutation in any of the gene related to reproductive processes (replication, transcription, etc.) can cause a ripple effect extending far beyond a single function, resulting in cataclysmic effects. The p53 gene, for instance, regulates cell division. This keeps cells from growing and dividing too quickly or in an uncontrolled manner through preventing transcription and activating p21 – a gene which inhibits cyclin dependent kinase, which hinders reproduction. If p53 has a mutation, none of this triggering would occur, and the cell would not go through apoptosis, but rather continue the cell cycle, making the mutation even more widespread. Not only this, but, also as we learned, the cancer cells would likely enter the bloodstream leading to even more tumors in numerous other areas.

Let’s continue this conversation—what are your thoughts on the intersection of CRISPR technology and cancer research?



Immune Evasion Unveiled: The Thrilling Genetic Drama of Tumor Suppressors and Their Sneaky Dance with Cancer Cells

Cancer, an unwelcome antagonist in our lives, often emerges as the thief of precious moments with our loved ones and friends. Ever wondered how it manages to disrupt the narrative of our lives, stealing the scenes we hold dear? Or perhaps, reflecting on those stolen moments, have you found yourself questioning the resilience of the human spirit in the face of such a formidable foe? Cancer perfectly reflects the quote that Alfred from  “The Dark Knight” said to Bruce  ‘Some men just want to watch the world burn”. In this case Cancer just wants to watch the world burn because it gains nothing.

Cancer stem cells text resized it

A study conducted recently at Howard Hughes Medical Institute by Stephen Elledge highlights the strange role played by altered tumor suppressor genes. Compared to the common belief that implies mutations in these genes only encourage unrestricted cell growth. The study revealed that in excess of 100 defective cancer suppressor genes in mice may impair the immune system’s ability to identify and eliminate cancerous cells.  Do you know how the immune system is able to detects and eliminate cancerous cells? If not this is how. The immune system is able to identify and eliminate the cancerous cells by using  T cells. These T cells constantly patrol the body to identify cells that display abnormal or mutated proteins on their surfaces. These proteins, known as antigens, can be indicative of cancerous changes. Dendritic cells then engulf and process abnormal proteins from cancer cells. They then present these antigens on their surfaces. They then present the cancer antigens to T cells.This activates specific T cells (cytotoxic T cells) that are capable of recognizing and targeting cells with the presented antigens. Activated cytotoxic T cells travel to the site of the cancer cells and release substances, such as perforin and granzymes, that induce apoptosis (programmed cell death) in the cancer cells. Successful elimination of cancer cells leads to the development of memory T cells. These memory cells “remember” the cancer antigens, providing a faster and more efficient response if the same cancer cells reappear. This challenges the conventional understanding that mutations in tumor suppressor genes primarily trigger unrestricted cell division. Instead, it suggests that such mutations can also impact the immune system’s ability to identify and eliminate cancerous cells through the T cell-mediated recognition process. This broader perspective underscores the complex interplay between genetic mutations, immune responses, and cancer development.

Tumor Growth

This has several key concepts that we covered in our AP Biology class, particularly related to cell regulation, cancer, and the immune system.

The immune system’s role in identifying and eliminating cancer cells is a significant aspect of the AP Biology curriculum. The discussion of T cells, dendritic cells, and the process of presenting cancer antigens aligns with the immune system’s functions and responses to abnormal cells. This aligns with what we learned in AP Bio regarding the immune system’s crucial role in defending the body against abnormal or potentially harmful cells, including cancerous cells because we got to see how the T Cells, Dendritic Cells, and Memory T Cells really work. We also got to see how the immune system also works directly with blood sugar levels. With various activities in class with the skittles as glucose and how the pancreases would either send a message to produce insulin or  glucagon depending on which the body needed to maintain a balanced blood sugar level.

 

Cancer: What Can We Do to Treat It?

We’ve talked about many viruses before and how they affect our bodies. However, what we’re talking about today is not  a virus, but when people get it, it’s scarier than most viruses. It is called Cancer.

Breast cancer cell (2)

There are currently more than two hundred cancers around the globe, and depending on the severity of the Cancer, the treatment is also determined. Cancer, unlike a virus, is where the cells divide uncontrollably. In addition, it also tricks the cells inside our bodies into creating new blood vessels to feed the tumor cells to generate more. Our cells and blood vessels will eventually attack these cells, forming tumors. Once the tumor gets big enough, it can divide and move to different parts of your body, and if the tumor is on some vital organs, it can suppress those organs, eventually leading to death.

The current methods to treat cancers are chemotherapy, radiation, or surgery. The first two methods aim to kill tumors that are potentially growing and spreading to different parts of your body. However, if the tumor is not that big, the doctors might suggest surgery to remove the tumor located in a particular area of your body. At the end of the day, it’s about stopping the uncontrollable cell division that’s happening inside of your body.

One good piece of news is that nowadays, we have the technologies to not only give our treatments to more people who suffer from cancer, but we also can cut out the energy supply to those cancer cells.

Can Cancer Cell’s Medication Immunity Be Stripped?

Cancer is one of the hardest diseased to fight. If a tumor begins to grow inside of a patient, they may be given drugs to fight off the corrupt cells. The problem with this is that the cancer cells could become immune to these drugs. Through the use of CRISPR. In Novel Crispr imaging technology reveals genes controlling tumor immunity, a new way of fighting cancer is revealed. Instead of targeting the whole tumor, Perturb-map marks cancer cells and the cells around cancer cells. Once this is completed, it is able to identify genes controlling cancer’s ability to become immune to certain drugs.

Mitosis appearances in breast cancer

To fight cancer cells, scientists use thousands of CRISPRs at the same time. This identifies every gene in a sequence and allows them to be studied. Through Perturb-map, scientists can now dive deeper and find where the cell immunity to drugs originates. A certain pathway in the cell is controlled by the cytokine interferon gamma or IFNg, and a second is by the tumor growth factor-beta receptor or TGFbR. When the cell had a gene with TGFbR2 or SOCS1, the latter of which regulates IFNg, tumor cells grew. When the cell lacked one of these, it shrunk. Moreover, it was discovered that tumors with SOCS1 were susceptible to attacks by T cells, but TGFbR cells had immunity against them. This stayed true even when both types of cells lived in the same environment. With findings like these emerging more and more, the future of cancer treatment is looking brighter than ever.

Chromosome DNA Gene unannotated

Cell Cycle Regulation in Revolutionary Gene Editing Technique (a.k.a. CRISPR)

There are more than 500 different types of human cancers. Wouldn’t it be wonderful if scientists could develop cures for all of them? Scientists believe that CRISPR gene-editing can be used to cure some cancers. CRISPR (an acronym for clustered regularly interspaced short palindromic repeats) is a way of targeting a specific bit of DNA inside a cell which can then be gene-edited to change such bit of DNA. CRISPR has also been used for other purposes, such as turning genes on or off without changing their DNA sequence.

 

Recent research has found a link between CRISPR gene-editing and mutated cancer cells. Scientists believe that a further understanding of this link can identify a group of genes which should be monitored for mutations when cells are subjected to the CRISPR gene-editing method. Although CRISPR gene-editing holds promise for cell repair, the application of CRISPR gene-editing, which is meant to identify and correct damage in cells, can also cause damage to cells in a controlled manner. Such damage activates a protein, p53 (“also known as the guardian of the genome”), which helps repair damaged DNA. 

CRISPR-Cas9 mode of action

P53 is a transcription factor, which is a protein that regulates the rate at which DNA is transcribed into RNA. These transcription factors bind to regulatory sequences in proteins, thus changing the shape of DNA, ultimately making them the most vital form of gene regulation. Transcription factors include many proteins but exclude RNA polymerase, which pries two strands of DNA apart and joins two strands of DNA together (Campbell, 280). P53 works by sliding along the damaged DNA, seeking a critical site to which it attaches and then sends a message to halt cell division until the DNA is repaired. In other words, p53 acts as a checkpoint in the cell cycle, preventing cell from proceeding though the G1 and G2 phases of the cell division cycle. In mice, the same exact transcription factor exists; those that lacked the Trp53 gene developed tumors at a far faster rate than those with the functioning gene.

 

By using CRISPR technology to damage DNA at the same cite at which DNA damage occurs, scientists are able to identify the protein responsible for cellular proliferation. If damage to the cell is too severe then p53 triggers apoptosis (the death of cells which occurs as a normal and controlled part of an organism’s growth or development) so that the damaged cell is destroyed. However, sometimes p53 is itself damaged which prevents such protein from binding to the damaged DNA in order to repair it or otherwise signaling destruction of the cell. When this occurs, the damaged cells multiply and grow, resulting in tumors. Scientists have found alterations in p53 in more than half of all cancers and thus, consider p53 the most common event in developing cancer.

 

New studies show that p53 inhibition can make CRISPR more effective thus, counteracting “enrichment” (the process of purifying cells for downstream applications such as qRT-PCR, cell polarizations ex vivo, or to enrich cells for use in a flow cytometry experiment) of cells with p53 mutations which has been observed to occur in cell cultures when such cells have been subjected to CRISPR. In other words, there is in vitro evidence that CRISPR technology causes harmful p53 mutations to be more prevalent in the population that has been subjected to the CRISPR technique. These findings suggest that there is a group of genes that should be monitored for mutations when the CRISPR gene-editing method is applied to cells. 

 

Cancer is a devastating disease that has taken the lives of many people. Members of my family have suffered and lost their battle to cancer (most recently my dear aunt this past weekend). CRISPR presents the possibility of finding cures to cancer which are specifically designed to target the particular genetic mutations that are unique to each individual. Perhaps, the cure to cancer will be achieved sooner than we realize,  although clearly not soon enough. 

 

Works Cited:

Reece, Jane B, and Neil A. Campbell. Campbell Biology. Boston: Benjamin Cummings / Pearson, 2011. Print.

Cellular GPS: A New Cancer Treatment

In recent years, it is estimated that 40% of people will face cancer during their lifetime. Still, there exist few reliable treatments for cancer, whereby it has become one of the leading causes of death in the world. Ideally, if a tumor is confined to one area of the body and is easily accessible, doctors may simply try to remove it with surgery. However, tumors are usually widespread and not so easily identifiable, whereby doctors turn to treatments such as chemotherapy which causes mass death of both healthy and unhealthy cells throughout the body. Nonetheless, scientists have discovered a potentially more targeted treatment for cancer, involving guiding magnetic seeds to tumors and burning them.

Bodily cells undergo the cell cycle, a controlled series of stages referred to as interphase, mitosis, and cytokinesis. Interphase is comprised of the G1, S, and G2 phases where cells perform normal activities, grow, undergo DNA replication, and duplicate organelles. Next, mitosis marks the division of the nucleus while cytokinesis marks the division of the cytoplasm. During this process, there are “checkpoints” at the end of the G1 phase, G2 phase, and mitosis. For example, maturation-promoting factors may trigger a cell’s passage through the G2 checkpoint if it has successfully duplicated and grown or stop a cell’s passage through this gateway if it has incorrectly copied itself. Cancer is caused when mutations in certain genes cause uncontrollable cell growth; this unchecked and rapid division causes many cells to pack closely together into tumors which hijack bodily functions, ultimately proving fatal unless treated.

Recently, researchers have proposed a new method to treat cancer patients, especially those with tumors in hard-to-reach places like the cranium. This treatment would send a highly magnetic thermoseed into one’s body which would be remotely heated once at the site of the tumor. Here, like driving a car on a loopy road, a doctor would use an MRI scanner to carefully guide the magnetic seed through the patient’s body. MRI scanners are reliable tools in scanning the location of tumors, so they would accurately pinpoint where to target and where to avoid with the thermoseed. Thus, this controlled method of eradicating tumors poses less of a threat with regard to damaging the body as a whole or even damaging surrounding tissues.

Although the prospect of such innovative research for remedies fuels optimism, it surely raises the question of which patients should undergo the new thermoseed treatment rather than well-trusted treatments like chemotherapy or open surgery. According to the study, this method would be greatly influential in treating glioblastoma, a common brain cancer. With traditional open brain surgeries, patients merely survive a year to a year and a half on average. Moreover, side effects are always a large risk with many current cancer treatments. However, I believe that killing the tumor remotely with a thermoseed and MRI has the potential to be a breakthrough, successfully eliminating the tumor and posing fewer long-lasting effects. While this treatment is still an idea at the beginning stages of research, its projected benefits make me optimistic about its future.

What do you think? Will this proposed cancer treatment be the reliable cure scientists have been looking for or a futile treatment that only reminds us of the challenge we are up against?

Can Fruit Flies Really Help Cancer Research?

Fruit fly (7424411436)In a study conducted at the University of California, Berkeley, researchers identified similarities between fruit flies and humans with cancer and believe this research could lead to prolonging the lives of cancer patients. Cancer, a disease where cells “grow uncontrollably and spread”, was diagnosed in 18.1 million new cases and claimed the lives of 9.5 million new patients worldwide as recently as 2018. The Berkeley researchers took a new approach to tackle cancer by “launching an attack against the destructive chemicals cancer is throwing off.” They believe this new method could increase patients’ survival rate and overall health.

David Bilder, a UC Berkeley professor, stated that the goal of the research was “to help the host deal with the effects of the tumor, rather than killing the tumor itself”; this represents a different approach to cancer treatment since most current treatments focus on killing the tumor and the unhealthy cells. Conventional treatments create serious side effects in patients as the treatments impact healthy cells too. Bilder’s research attempts to interfere with the blood-brain barrier, a feature of the central nervous system which is key in regulating microorganism entry and exit from the bloodstream and interstitial brain fluid. It is believed that inflammation caused by tumors leaves the blood-brain barrier open, but interfering with that process might slow tumor growth allowing for improved patient quality of life and life expectancy. This process could eliminate the need for toxic drugs that harm healthy cells while targeting cancer cells.

During the research a few years ago, Bilder’s team also learned some interesting new information about the impact of insulin on cancer. They concluded that tumors in fruit flies release a substance that blocks the effects of insulin. Insulin, a type of protein that coordinates organism activities while maintaining normal blood glucose levels, is a crucial component of our body system. It allows cells to absorb glucose which can serve as energy or convert to fat if necessary. Without insulin, cells are unable to use glucose as fuel and bodies would start breaking down their fat and muscle resulting in weight loss. This can pose an issue because it could lead to cachexia (an effect of cancer where patients are unable to maintain weight) which sadly kills ⅕ of cancer patients. Although more research is needed to investigate the relationship between insulin and cancer in humans, sugar may play a role in the growth of cancer.

 

CSIRO ScienceImage 355 Representation of Insulin Structure

Insulin Structure

I believe that this new approach to cancer treatment is a fascinating angle to effectively treat cancer patients. As someone who has experienced cancer in two close family members, I know firsthand how draining the treatments are because they target healthy cells as well as cancerous ones; this treatment simply diminishes these side effects. As Bilder states, “We think this is a real blind spot that hasn’t allowed scientists to address questions about how the tumor is actually killing outside of its local growth.” It could offer a “complementary way of thinking about therapy.” It is great to see new ways of thinking address a disease that impacts so many people.

Migrating Cancer Invading the Brain

Glioblastoma tumor Credit: The Armed Forces Institute of Pathology [Public domain]

Recent research has unveiled the ability of cancer cells to invade and take over our brain’s neural network. Three independent studies, Monje, Winkler, and Hanahan have indicated that not only can cancer cells metastasize to parts of the body, including the brain, but once present, they have the uncanny ability to “hijack” our brain and incorporate into our neurons.  The research published in Nature discovered this unusual ability in a certain type of brain cancer called gliomas and in specific aggressive breast cancers that are known to spread to the brain, called Triple Negative Breast Cancer. This accidental discovery was “crazy stuff” according to Winkler, and researchers were not only amazed by their findings, but found it difficult to believe.  The implications of the research hold great promise for treating aggressive forms of cancer in the future.

The  first discovery was made by Winkler’s team and supported by Monje, found that synapses in the tumors themselves, specifically in glioma samples, are a type of cancer that is known to be difficult to treat.   Synapses are usually used for neural cell communication, but the discovery of them in tumor cells was novel.  The synapses seem to play a role in allowing the cancer cells to grow and thrive.  This discovery indicates that cancer’s ability to “weave into the brain’s neural network” explains why these cancers have been so difficult to detect early on and treat successfully.  Rather than disrupting the brain’s functions, the tumor incorporates itself into the brain’s normal functions, becoming a stealthy “hijacker”.

In a third study, Hanahan expanded the results from not only brain cancers but also certain types of aggressive breast cancers that are known to spread to the brain.  They found that certain breast cancer cells actually invade the brain and take on a role similar to neurons.  These triple-negative tumors had the uncanny ability to turn on genes that play a role in signaling between neurons.  They specifically found the cancer cells to have the ability in the brain to create a specialized type of synapse that can take in a large amount of Glutamate, one of our brain’s main neurotransmitters.  Glutamate not only functions as a neurotransmitter, relaying signals between neurons, but also seems to play a role in tumor growth.

Lisa Sevenich, a scientist studying brain cancer, emphasized how hostile the brain’s environment is for cancer cells, and the ability of these glioma cells to survive and even thrive in the brain highlights their adaptability and resilience.  Researchers looking forward hoping that these unusual cancer cells may hold promise for new innovative treatments for cancer in the future.

 

 

 

 

 

Cancer and Fruit Flies

 

 

Photo by Malcolm NQ from Flickr

A recent study has found a way to track each step of a healthy cell as it becomes cancerous. Researchers were able to study the “genes and molecules involved in each step.”

The researchers provoked genomic instability in the cells of the fruit fly’s wing, or the Drosophila melanogaster, and allowed these cells to withstand the organism’s natural defenses. The scientists were able to see the cancer spreading throughout the cell and invading nearby organelles and cell structures. According to one scientist, Andres Dekanty, “for the first time we have a genetic model that allows us to understand the events that take place, starting from when cells begin to accumulate genomic errors until the development of a tumor.”

Furthermore, the researchers at the Institute for Research in Biomedicine believe that their research will be important for determining if cancer is caused by genomic instability. If this proves to be true, scientists and doctors will have a specific target to study, and to treat.

Researchers believe that the key to curing caner is identifying the difference between normal, healthy cells and a cell with genomic instability. Dekanty hopes that since “there isn’t a treatment available that attacks only the cells with genomic instability, if we can clearly differentiate one from the other, we’ll hopefully be able to find drugs that target them specifically.”

This study is of major importance because today, cancer treatments, such as chemotherapy have many side effects because they aim to stop cell division in both infected and healthy cells.  New, more precise treatments could stem out of this study.

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