Personalized Medicine: Tailoring Cancer Treatment Through Genetics

Next generation sequencing (NGS) is reshaping our understanding of breast cancer, and in this episode, Saanvi D shares her personal connection to this vital topic. Her journey began when her aunt, one of her closest friends, was diagnosed with breast cancer, which opened her eyes to the impact of genetics on their lives. Saanvi D dives into how NGS work—allowing scientists to sequence millions of DNA fragments at once—and its significance in identifying mutations like BRCA1 and BRCA2. This technology not only pinpoints genetic changes that may influence cancer treatment but also helps in discovering potential therapeutic targets and monitoring disease progression. By the end, Saanvi D hopes you'll see how NGS is more than just a scientific advancement; it offers real hope for patients and families facing the challenges of breast cancer.

Episode Transcript

(00:04):
Welcome to Sequencing Hope,the podcast where we explore how
the latest advances in biologyare transforming lives.
My name is Sanvi and I'm ajunior at Detroit Country Day Upper
School, and today we're goingto take a deep dive into the world
of next generation sequencingand the breast cancer gene.
Before we dive into thescience of genetic testing, I want
to share a little bit on whygenetic testing for hereditary disease
means a lot to me.

(00:24):
I remember coming home fromfifth grade camp to find out that
my aunt, who was who was alsoone of my best friends, was diagnosed
with breast cancer.
It was a shock to our family.
Suddenly, terms like BRCA1mutation, genetic testing, and risk
assessment became part of oureveryday conversations.
Watching her go through all ofit, the diagnosis, treatment and
recovery made me realize howquickly our lives can change simply

(00:46):
due to genetics.
This experience sparked mypassion for understanding the science
behind cancer and howinnovations like next generation
sequencing can change outcomesfor families like mine.
Now let's explore the biologybehind this Breast cancer is a disease
caused by changes in our DNA.
Among the most well knownmutations are in the BRCA1 and BRCA2

(01:07):
genes.
These genes normally helprepair damaged DNA, acting as guardians
of our genome when they're mutated.
This repair process fails,increasing the risk of cancer.
But how do scientists detectthose mutations?
Enter next generationsequencing, otherwise known as ngs.
This technology hasrevolutionized genetics by allowing
us to sequence millions of DNAfragments simultaneously, rather

(01:29):
than one gene at a time inolder methods.
So how exactly does NGS work?
Let's break it down.
The first step is sample collection.
This is when DNA is extractedfrom a patient's blood or tumor tissue.
The second step is library preparation.
The DNA is fragmented intosmall pieces and special adapters
are attached to each fragment.

(01:50):
The third step is sequencing.
These fragments are loadedonto a sequencing machine.
The machine reads the sequenceof adenine, thymine, cytosine and
guanine in each fragment.
The last step is data analysis.
Powerful software aligns thesesequences to reference human genome
identifying mutations or variations.

(02:10):
NGS can analyze entiregenomes, exomes or targeted gene
panels relevant to breast cancer.
This approach uncovers notonly BRCA mutations, but also other
genetic changes that mayinfluence cancer risk or treatment
response.
A 2012 review by Desmet andSoderu, in Current Opinion Oncology,
shows how next generationsequencing has fundamentally transformed

(02:32):
breast cancer research andclinical understanding.
By sequencing hundreds ofbreast tumors, researchers uncovered
not only new cancer drivinggenes, often called driver mutations,
but also demonstrated thatmutations, while individually rare,
frequently converge on commoncellular pathways that drive cancer
progression.
This means that even if twopatients have different mutated genes,

(02:52):
those genes might disrupt thesame biological process such as cell
cycle control or DNA repair,which is crucial for designing targeted
therapies.
NGS also helps scientistsdiscover the concept of intra tumor
heterogeneity, the process ofgenetically distinct subpopulations
of cancer cells within asingle tumor.
The review highlights that inevery tumor studied there's typically

(03:13):
a dominant clone comprising atleast half of the tumor cells alongside
numerous sub clones withunique mutations.
This structure is extremelyimportant because it helps explain
why some cancers relapse orresist treatment as therapies may
eliminate the dominant clonebut allow resistant subclones to
survive and proliferate.
Most importantly, NGStechnology can detect not only point

(03:35):
mutations but but also biggervariations such as gene fusions and
chromosomal rearrangements bysequencing both ends of DNA fragments.
This approach allows for theidentification of fusion genes and
splice variants which can becritical drivers of cancer and potential
therapeutic targets.
NGS can also be applied tocell free DNA in plasma which enables

(03:55):
non invasive monitoring oftumor specific DNA arrangement.
The strategy helps to trackdisease progression and reoccurrence
in real time.
Recently, Pisclio in Cancersshowed the clinical impact of NGS
by showing how it is used toidentify actionable mutations beyond
BRCA1 and BRCA2 such asPike3CA, TP53 and ERBB2.

(04:17):
Their study used gene panelsto analyze breast cancer samples
which revealed that certainmutations like those in Pike3CA are
now targetable with FDAapproved inhibitors.
This discovery provided newtreatment options for patients with
hormone receptive positivebreast cancer.
Next arrangement Sequencing isnot just a research tool, it's a
clinical game changer.
So what exactly are some ofthe ways that NGS has changed the

(04:39):
field of medicine?
Personalized Medicine NGSenables doctors to tailor treatment
based on patients unique genic profile.
If a mutation in Pike3CA or ESR1 is found, targeted therapies can
be prescribed thatspecifically block those pathways,
improving effectiveness andreducing side effects.
Risk assessment and preventiondetecting BRCA1 or BRCA2 mutations

(05:03):
allow family members toundergo genetic counseling and testing.
This can lead to preventativemeasures such as enhanced screening
or prolific surgeries,significantly reducing cancer risk
monitoring and early detection.
Liquid biopsies using NGS candetect circulating tumor DNA in blood,
allowing for real timemonitoring of disease progression
or reoccurrence withoutinvasive procedures.

(05:25):
Access to clinical trialsPatients with rare or novel mutations
can be matched to clinicaltrials testing new drugs, providing
hope where standard treatmentsfall short, imagine a future where
every cancer patient receivesa genetic roadmap guiding their care
from the moment they arediagnosed through recovery.
That future is rapidlybecoming a reality, thanks to ngs
Reflecting on my aunt'sjourney, I realize how far we've

(05:48):
come and how much hopetechnology like NGS offers.
While she faced uncertaintyback then, today's patients have
access to powerful tools thatcan change their prognosis.
But challenges remain.
Access to NGS is not universaland many mutations still lack targeted
therapies.
It is vital that researchcontinues to be conducted and education
continues to be provided.

(06:09):
As we wrap up today's episode,I hope you've gained a deeper understanding
of how next generationsequencing is not just a technological
marvel, but a true gamechanger in the fight against breast
cancer.
Thank you for joining me onSequencing Hope.
Remember, behind everyscientific breakthrough, there are
real people and real stories.
Stories like my aunt's and somany more people's stories.
I'm Sanvi and I look forwardto exploring more stories of science

(06:32):
and hope with you next time.