Sunday, December 24, 2017
Monday, December 18, 2017
Steve Jobs
(Steven Paul Jobs was an American entrepreneur, business magnate,
inventor, and industrial designer. Jobs and Apple Co-Founder, Steve Wozniak, are recognized world wide as pioneers of the micro-computer revolution of the 1970s and 1980s; 1955-2011).
Diane Vreeland
(Diana Vreeland was a noted columnist and editor in the field of
fashion. She worked for the fashion magazines Harper's Bazaar and Vogue,
being the editor-in-chief of the latter, and as a special consultant at Costume Institute of the MET. She was honored in the Hall of Fame in 1964 under 'Internationally Best Dressed' list; 1903-1989).
Saturday, December 16, 2017
Constantine:Liquid Biopsy for Cancer Treatment
Based on the DC comic, ‘Hell-Blazer’, the 2009 film ‘Constantine’ tells
the life story of John Constantine (Keanu Reeves) who was born with a gift- or
as he calls it a ‘curse’. As a suicide survivor, he is haunted by his horrific
memory spent in Hell when he is pronounced dead for a full 2 minutes, gives
Constantine his current ambition to use this supernatural ‘talent’ to hunt down
demons and earn his spot in Heaven. Having smoked 2 packs of cigarettes since the age of 15, Constantine
discovers that he has less time on earth than he thought. It is without a doubt
that if current breakthroughs in cancer treatment with liquid biopsies, that
our protagonist would have more time to earn his way into God’s good graces and
ultimately into Heaven.
INTRODUCTION:
Over a century has passed since the discovery that tumors
shed molecules and cells into the fluids throughout the body. Even more
recently, it was discovered that analyzing these very same molecules and cells
reveal similar information that tissue biopsies have given to the world.
Researchers from diverse backgrounds have worked relentlessly to develop,
refine, and establish clinical uses for liquid biopsy tests. [A]
These dedicated individuals have been continually exploring
new approaches to enhance the benefits of current cancer treatments. One of
these approaches has been focused on enhancing the main form of treatment-using
just tissue biopsies. This procedure is known as ‘liquid biopsy’. It relies on
analyzing bits of tumor material (molecules and whole cells) found in
circulating blood, various body fluids, urine, cerebrospinal fluid, and or even
saliva. These liquid biopsy tests analyze the many and various types of tumor
material like DNA, RNA, proteins, exosomes, and whole cells. [A]
Majority of bodily fluids are easy to access and are
therefore the most common procedure for collecting sample(s). This key feature
makes liquid biopsies our greatest weapon in treatment of cancer as it can be
used in various important applications where with tissue biopsies it would be
much more difficult to conduct. Liquid biopsies are being used to monitor
cancer development, track an individual’s response to treatment, or serve as a
form of surveillance method for those who have completed their treatment but
remain at high risk of their disease returning. [A]
Increasing treatment options for patients increases their chances of winning the battle against cancer. It is studies such as these where scientists make discoveries that lead to more precise robust analysis of circulating molecules, cells, and everything in between. The recent observations that have been made is dictating the variety of technology emerging and exciting clinical potential for liquid biopsy approaches. [A]
Routine pre-screening processes should include liquid
biopsy tests for people visiting their primary care physician. This minor yet
pivotal addition can detect early-stage cancer and possibly save countless
lives. There are high risk individuals who were born with hereditary cancer
syndromes and will most likely have no conscious awareness of this until it is
too late. The hope for the future is to use liquid biopsy tests along with
existing technology to help detect and personalize treatment to the road of
recovery.
BACKGROUND INFORMATION:
When a patient has a
suspicious lump or symptoms, one of the first things a physician may do is
perform what is known as a ‘tissue biopsy’. This procedure collects cells from
the body for closer inspection. Examining the appearance of the cells under the
microscope can determine A) presence or absence of cancer, B) the type of
cancer detected, and C) give physicians the necessary clues for a starting
point in constructing a patient’s prognosis. Tumors release pieces
of DNA into the bloodstream that can be analyzed to obtain important
information that may inform patient care. The molecular analysis of a tissue
biopsy can give physicians the necessary information to create personalized
treatment for each unique potential cancer patient.
Most cancer types have unknown specific DNA mutations
and/or well-established biomarkers that allow scientists to identify then track
the disease with ctDNA. Many studies use liquid biopsy tests to detect ctDNA in
samples of blood collected from patient’s months before they were diagnosed
with cancer by traditional methods, like imaging techniques. But, just because
ctDNA is in the blood, this does not always mean that this ctDNA represents the
DNA from the tumor.
Tumors are heterogeneous, meaning that their DNA mutations vary between cancer cells in a tumor. Even when diagnosing the same cancer type, DNA mutations in cancer patients vary case by case. This makes identifying ctDNA biomarkers incredibly difficult to treat let alone cure. It is unknown whether ctDNA is released from the whole tumor or only certain parts of it.
Typically, biomarkers are used to track advanced pancreatic cancer, but they are considered unreliable for early detection. The technology for detecting ctDNA in body fluids has improved dramatically, but the understanding and knowledge needed to identify the appropriate biomarkers of numerous forms of cancer have not.The earlier the detection the more successful a patients’ outcome, but tissue biopsy tests are very difficult for patients.
These tests are invasive, high risk, and painful. The process involves a large needle, known as an ‘endoscope’ and in some cases, open surgery is also needed. Then there are those cases in which patients cannot even have a tissue biopsy performed on them because of the location of the tumor(s) and/or other health conditions. Unfortunately for cancer patients today, this is the most effective approach modern science has in the detection and method in obtaining information about cancer.
Mark Roschewski, M.D., of NCI's Cancer Research Center and
his colleagues found that alterations of ctDNA were linked to positive
responses in chemotherapy. Scientists realized that patterns of ctDNA
were detecting tumors during their growth periods much quicker than CT scan(s)
were. This revealed the level of sensitivity liquid biopsy tests have compared
to our current imaging techniques such as CT scans.
Tumors are heterogeneous, meaning that their DNA mutations vary between cancer cells in a tumor. Even when diagnosing the same cancer type, DNA mutations in cancer patients vary case by case. This makes identifying ctDNA biomarkers incredibly difficult to treat let alone cure. It is unknown whether ctDNA is released from the whole tumor or only certain parts of it.
Typically, biomarkers are used to track advanced pancreatic cancer, but they are considered unreliable for early detection. The technology for detecting ctDNA in body fluids has improved dramatically, but the understanding and knowledge needed to identify the appropriate biomarkers of numerous forms of cancer have not.The earlier the detection the more successful a patients’ outcome, but tissue biopsy tests are very difficult for patients.
These tests are invasive, high risk, and painful. The process involves a large needle, known as an ‘endoscope’ and in some cases, open surgery is also needed. Then there are those cases in which patients cannot even have a tissue biopsy performed on them because of the location of the tumor(s) and/or other health conditions. Unfortunately for cancer patients today, this is the most effective approach modern science has in the detection and method in obtaining information about cancer.
“John Constantine: Detective. What if I
told you that God and the devil made a wager, a kind of standing bet for the
souls of all mankind?
Angela Dodson: I'd tell you to stay on
your meds.
John Constantine: Humor me. No direct
contact with humans. That would be the rule. Just influence. See who would win.
Angela Dodson: Okay, I'm humoring you.
Why?
John Constantine: Who knows. Maybe just
for the fun of it. No telling.
Angela Dodson: Oh, so it's fun? It's
fun when a man beats his wife to death? It's fun when a mother drowns her own
baby? And you think the devil is responsible? People are evil, Mr. Constantine.
People.
John Constantine: You're right. We're
born capable of terrible things, but then sometimes something else comes along
and gives us just the right nudge.
Angela Dodson: Well, this has been real
educational, but... I don't believe in the devil.
RESEARCH:
Since ctDNA-based liquid biopsies are non-invasive and
can be easily repeated, this makes them our greatest weapon against cancer.
They carry the potential to become the most effective tools in monitoring
patients’ status pre- and post-treatment. By tracking patients’ response to
treatment, clinicians will be able to adjust aspects of treatment accordingly.
This potential alternative tested ability of liquid
biopsy to test the track treatment responses in patients with lymphoma. They
were able to detect these changes in ctDNA levels in patients within 14 days
from the start of immuno-therapy treatment. With early detection, patients’ odds
of beating cancer increase. Especially with the fact that only a small portion
of individuals respond to immuno-therapy. From another division of NCI, a division of cancer treatment
and diagnosis, Brian Sorg, Ph.D, used this new information to help track the
development of drug resistance during treatment.
When looking at many of lung
cancer patients’ responses to treatment, which includes a class of drugs known
as ‘tyrosine kinase inhibitors’ that help the body develop resistance to
treatment. This resistance lasts from 1 to 2 years.
These results led to further studies which analyzed ctDNA
mutations of lung cancer patients who during treatment became resistant to
‘tyrosine kinase inhibitors’. These individuals, roughly 80% of participants,
developed the genetic mutation that caused this resistance. However, to really
determine whether liquid biopsy test(s) can truly identify the tumors with this
mutation as well as those who will most likely benefit from which
treatment.
Liquid biopsy tests have the added advantage of providing molecular information about the cancer, which can change during and after treatment. Precision Medical treatments could also benefit from ‘ctDNA-based liquid biopsies’ by identifying unique molecular characteristics of cancer that is developing and growing inside of patients'.
Liquid biopsy tests have the added advantage of providing molecular information about the cancer, which can change during and after treatment. Precision Medical treatments could also benefit from ‘ctDNA-based liquid biopsies’ by identifying unique molecular characteristics of cancer that is developing and growing inside of patients'.
Cancer Center of UC San Diego Moores has analyzed 168 blood
samples from patients each with a different type of cancer -locating in the
brain, breast, lung. They discovered that in 58% of the participants at least
one cancer related ctDNA mutation. Most of these patients, a Food and Drug
Administration (FDA)–approved drug was available to treat cancers with that
mutation.
There also exists many other studies which demonstrate the practicability of ctDNA-based liquid biopsies applied on a large scale to identify DNA mutations in patients' cancers. Investigators used Guardant360 to detect mutation in ctDNA of over 15,000 patients. The Guardant360 is a test which can analyze 70 cancer-related genes in a blood sample. Most of these patients had genetic mutations identified by the liquid biopsy test. This observation was consistent with the genetic mutations found by tissue biopsy test.
There also exists many other studies which demonstrate the practicability of ctDNA-based liquid biopsies applied on a large scale to identify DNA mutations in patients' cancers. Investigators used Guardant360 to detect mutation in ctDNA of over 15,000 patients. The Guardant360 is a test which can analyze 70 cancer-related genes in a blood sample. Most of these patients had genetic mutations identified by the liquid biopsy test. This observation was consistent with the genetic mutations found by tissue biopsy test.
Currently there are many liquid biopsy tests available but
still need to be tested for possible risks or side effects and what possible
clinical benefits might be seen in patients. The FDA officially approved a type
of liquid biopsy test in 2016 which detects the EGFR gene mutation(s) in ctDNA
in lung cancer patients. This test is better known as the ‘EGFR Mutation Test’ or
‘Cobas’
It was created with the intention of identifying good candidates for
‘erlotnib’(Tarceva) and ‘osimeritinib’(Tagrisso) treatments. These treatments
are targeted therapies that attack cancer cells with EGFR mutations. However,
the test can produce a false-negative test result, the FDA has recommended a
tissue biopsy if the liquid biopsy is negative (meaning it does not detect an EGFR
mutation).
CONCLUSION:
The field of cancer research has seen much progress, but
now there exists a possible solution by combining tissue and liquid biopsies.
First, a tissue biopsy could be used to identify unique biomarkers for an
individual’s tumor, then liquid biopsy tests could be used to track those
biomarkers. However, it is critical to note that ctDNA itself may not be the
best source of information regarding clinical decisions.
As of right
now, it is the risk of ‘over treatment’ in early cancer development that gives
scientists and researchers their greatest concern. There were instances in
these studies where ‘liquid biopsy tests’ revealed cancerous DNA when no cancer
was present producing false-positive test results. These tests can detect
early-stage tumors that will grow so slowly that in many cases will have no
harm let alone effect on the individual if the tumor grows at all.
“Satan: Hello, John. John, hello.
You're the one soul I would come up here to collect myself.
[claps giddily]
There the potential in ctDNA-based liquid biopsies is
there, but limitations are also present when using this treatment method.
Scientists are also unsure of whether mutations found in ctDNA are ‘driver’
mutations which play the major role in cancer’s biology. They could instead be
the ‘passenger’ mutations, where the alterations that occur along with the
development of cancer but have no control of its growth.
To really determine that finding ctDNA in a patient’s blood can be an accurate marker for early-stage cancer, possibility of this detection to authorize treatment(s) and if this innovative treatment improves patient outcomes, more prospective cohort studies are needed.
The NCI supports the initiative to develop and validate the possible technologies that liquid biopsy has to offer in detecting early-stage cancer. The organization also supports advancing the development in distinguishing cancer from benign conditions and to quickly identify slow growing cancers. A major aim of the initiative is to create a public–private partnership that brings engineering and clinical experts together to accomplish these goals.
To really determine that finding ctDNA in a patient’s blood can be an accurate marker for early-stage cancer, possibility of this detection to authorize treatment(s) and if this innovative treatment improves patient outcomes, more prospective cohort studies are needed.
The NCI supports the initiative to develop and validate the possible technologies that liquid biopsy has to offer in detecting early-stage cancer. The organization also supports advancing the development in distinguishing cancer from benign conditions and to quickly identify slow growing cancers. A major aim of the initiative is to create a public–private partnership that brings engineering and clinical experts together to accomplish these goals.
[Gabriel
holds Constantine helpless]
“Gabriel: You're handed this precious gift,
right? Each one of you granted redemption from the Creator - murderers,
rapists, and molesters - all of you, you just have to repent, and God takes you
into His bosom. In all the worlds in all the universe, no other creature can
make such a boast, save man. It's not fair.
[leans
closer]
Gabriel: If sweet, sweet God loves you so, then
I will make you worthy of His love. I've been watching for a long time. It's
only in the face of horror that you truly find your nobler selves. And you can
be so noble. So, I'll bring you pain, I'll bring you horror, so that you may
rise above it. So that those of you who survive this reign of hell on earth
will be worthy of God's love.
John
Constantine: Gabriel,
you're insane!
Gabriel:
[smiles] The road to
salvation begins tonight. Right now.
[Gabriel
blows, sending Constantine crashing through the door]”
Many researchers agree that studies which analyze the
effect(s) of liquid biopsy tests for clinical outcomes are needed before they
can be used on actual patients. Since October of 2017 clinical trials by Stanford
University and NCI teams have already started to evaluate an overall survival
rate of patients (specifically adult patients with metastatic solid tumors) who
will be the recipients of this targeted therapy.
Links:
[A] https://www.cancer.gov/news-events/cancer-currents-blog/2017/liquid-biopsy-detects-treats-cancer
*Please note! These images are not mine. They were found on
various tumblr, pinterest, google image sites! If any are yours’ please let me
know so that I can give you credit for them! Also the people in the images have
no relation to the diseases, illnesses, or cancers I write about. Thanks so
much & enjoy~
*Quotes by: www.imdb.com/title/tt0360486/quotes
*Screen caps by: www.cap-that.com/constantine/?page=54
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