Promises
Targeted therapy is a type of cancer treatment that
specifically targets molecules or genes that are involved in cancer growth and
spread. In pancreatic cancer, targeted therapy can be used to inhibit the
activity of specific signaling pathways that are involved in tumor growth and
survival.
One of the key targets for targeted therapy in pancreatic
cancer is the epidermal growth factor receptor (EGFR). EGFR is overexpressed in
many pancreatic tumors, and drugs that target EGFR, such as erlotinib and
cetuximab, have been developed and tested in clinical trials. However, the
results of these trials have been mixed, with some showing modest improvements
in survival and others showing no benefit.
Another target for targeted therapy in pancreatic cancer
is the vascular endothelial growth factor (VEGF) pathway. VEGF is a protein
that promotes the growth of blood vessels that supply nutrients and oxygen to
tumors. Drugs that inhibit VEGF, such as bevacizumab and ramucirumab, have been
tested in clinical trials for pancreatic cancer, but again, the results have
been mixed.
Other targets for targeted therapy in pancreatic cancer
include the mammalian target of rapamycin (mTOR) pathway, the mitogen-activated
protein kinase (MAPK) pathway, and the phosphatidylinositol 3-kinase (PI3K)
pathway. Drugs that target these pathways, such as everolimus, trametinib, and
buparlisib, have been tested in clinical trials, but their efficacy has been
limited.
In summary, targeted therapy has shown promise in
pancreatic cancer, but its efficacy has been limited, and more research is
needed to identify new targets and develop more effective drugs. Combination
therapy approaches that target multiple pathways simultaneously may also be
necessary to improve treatment outcomes. Clinical trials are ongoing to test
new targeted therapy approaches and combination treatments in pancreatic
cancer.
Limitations
Despite the promise of targeted therapy for pancreatic
cancer, there are several limitations to its efficacy and widespread use:
1. Heterogeneity
of pancreatic cancer: Pancreatic cancer is a complex and heterogeneous disease,
with different subtypes and genetic mutations. Targeted therapies that are
effective in one patient may not work for another, making it challenging to
identify the appropriate target and develop effective therapies.
2. Resistance
to therapy: Cancer cells can develop resistance to targeted therapy over time,
limiting the effectiveness of the treatment. Resistance can arise through
various mechanisms, including changes in the target molecule or activation of
alternative pathways.
3. Toxicity:
Targeted therapies can have significant side effects, such as skin rash,
diarrhea, and liver toxicity. In some cases, the toxicity can be severe enough
to require discontinuation of the treatment.
4. Cost:
Targeted therapies can be expensive, limiting access to patients who cannot
afford them or do not have insurance coverage.
5. Limited
benefits: While targeted therapies have shown promise in some cases, their
overall benefit in pancreatic cancer is limited. Most targeted therapies
provide only modest improvements in survival or progression-free survival, and
many patients still succumb to the disease.
In summary, while targeted therapy has the potential to
improve treatment outcomes in pancreatic cancer, its efficacy is limited by the
heterogeneity of the disease, the development of resistance, toxicity, cost,
and limited benefits. Further research is needed to identify new targets and
develop more effective therapies that can overcome these limitations.
What Targeted Therapies Are Available for Pancreatic
Cancer?
There are several targeted therapies approved by the Food
and Drug Administration (FDA) for certain groups of pancreatic cancer patients:
·
Erlotinib
·
Sutent® (sunitinib) for neuroendocrine
tumors
·
Afinitor® (everolimus) for neuroendocrine tumors
·
Vitrakvi® (larotrectinib)
·
ROZLYTREK® (entrectinib)
·
Lynparza® (olaparib)
For many of these treatments, patients must have testing
to see if they have mutations (changes) targeted by these treatments. This
testing includes:
·
Genetic testing for an inherited mutation:
testing of blood or saliva to find mutations the patient was born with, passed
on from a parent
·
Molecular profiling: testing of tumor tissue to
find mutations in the tumor (also known as tumor biomarker testing)
Erlotinib
Erlotinib, in combination with the chemotherapy gemcitabine
(Gemzar), is approved for use in advanced pancreatic adenocarcinoma (the most
common type of pancreatic cancer) that cannot be removed by surgery.
Erlotinib is not commonly used to treat pancreatic
cancer. This is because only a small group of patients benefited in clinical
trials.
Common side effects of erlotinib include
acne-like skin rash, diarrhea, nausea, appetite loss and fatigue.
Lynparza (olaparib)
Lynparza is FDA-approved as a maintenance therapy for
patients who have:
·
Stage IV pancreatic adenocarcinoma (the
most common form of pancreatic cancer)
·
Germline mutations (changes they were born
with) of BRCA (BRCA1 or BRCA2)
·
Stable disease (no tumor growth) after getting a
platinum-based chemotherapy as their first treatment
A patient can learn if they have a germline BRCA mutation
through genetic testing. About 4-7% of pancreatic cancer patients have germline
BRCA mutations.
Lynparza is a type of targeted therapy called a PARP
inhibitor. It blocks the PARP protein, which helps cells repair DNA damage.
This causes damage to build up.
Patients who have a BRCA mutation may respond well to
treatment with a PARP inhibitor like Lynparza because these mutations already
weaken the cells’ ability to fix damaged DNA. When too much DNA damage occurs,
the cancer cells cannot survive.
Approved as a maintenance therapy, the
goal Lynparza is to extend the time that a patient’s cancer does not progress
after receiving a platinum-containing chemotherapy. Common platinum
chemotherapies include oxaliplatin and cisplatin. Not all standard of care
chemotherapies for pancreatic cancer contain platinum agents.
Chemotherapy can cause side effects that may make
long-term use challenging. So, patients whose cancer has remained stable on
chemotherapy sometimes stop treatment entirely to give their bodies a break or
go on a maintenance therapy like Lynparza.
Common side effects of Lynparza include
lowered blood cell count, nausea, vomiting, diarrhea, fatigue, upper
respiratory tract infection and joint or muscle pain.
Vitrakvi (larotrectinib) and ROZLYTREK (entrectinib)
Two targeted therapies are FDA-approved for use in patients
with any type of locally advanced or metastatic solid tumor with an
NTRK gene fusion:
·
Vitrakvi (larotrectinib)
·
ROZLYTREK (entrectinib)
NTRK gene fusions are very rare in pancreatic cancer.
Only about 0.5% of patients have them. Patients can learn if they have an NTRK
gene fusion through molecular profiling.
Common side effects of these treatments
include fatigue, vomiting, constipation, dizziness, diarrhea and nausea.
Targeted Therapies for Pancreatic Neuroendocrine
Tumors (PNETS)
Two targeted therapy drugs are approved for the treatment
of advanced pancreatic neuroendocrine tumors (PNETs) that have
progressed and cannot be treated with surgery:
·
Sutent (sunitinib)
·
Afinitor (everolimus)
About 7% of pancreatic tumors are neuroendocrine tumors.
Both Sutent and Afinitor are taken as a daily pill.
Common side effects of Sutent include
lowered blood cell counts, diarrhea, upset stomach, nausea, vomiting, mouth
sores, loss of appetite, fatigue and congestive heart failure.
Common side effects of Afinitor include
lowered blood cell counts, fatigue, nausea, diarrhea, cough, mouth sores, high
blood sugar and pneumonitis (inflamed lung tissue).
Sources and Additional Information:
https://pancan.org/facing-pancreatic-cancer/treatment/treatment-types/targeted-therapy/
https://www.cancer.org/cancer/pancreatic-cancer/treating/targeted-therapy.html
