POPDC1 as a Potential Therapeutic Target in Various Cancers

This report examines POPDC1, a protein with potential as a therapeutic target for multiple cancers. It discusses clinical trial results, drug development strategies (including drugs like Ipilimumab and Brentuximab vedotin), and the importance of the FDA's breakthrough therapy designation. The report addresses necessary considerations like preclinical studies and potential side effects, emphasizing the immune-mediated adverse reactions that can occur. It highlights POPDC1's role in breast cancer, where its presence inhibits malignant phenotypes, and its impact on other cancers like hepatocellular carcinoma. Dosage recommendations for melanoma treatment are provided, along with an explanation of the Popeye domain's role in POPDC1 function. The report concludes by identifying gaps in current research, particularly regarding the mechanisms through which POPDC1 controls cell proliferation and migration, and emphasizes the need for further investigation to facilitate targeted therapeutic development. This analysis provides a comprehensive overview of POPDC1's therapeutic promise and the challenges that remain.

Running head: POPDC1 AS THERAPEUTIC TARGET FOR CANCER 1
POPDC1 as A Potential Therapeutic Target in Multiple Cancers
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POPDC1 AS THERAPEUTIC TARGET FOR CANCER 2
POPDC1 as A Potential Therapeutic Target in Multiple Cancers
Recommendations
1. What is needed next?
So far the POPDC1 protein therapeutic drug have been tested and confirmed to work for
cancer. The drug usage should rely on the breakthrough therapy designation which is a process
designed by the FDA (food and drug administration) to review and expedite drugs intended to
cure serious conditions when clinical evidence demonstrates that the drugs have substantial
improvement on available therapies based on endpoints that are clinically significant.
2. what about preclinical studies,
Since clinical trials have been done under conditions that vary widely, the adverse rates
of reaction observed should not be compared directly with the rates in other clinical experience
or trials with therapeutics in similar class as they may not reflect the reaction rates that are
observed in the clinical practice. So far adverse reactions that are clinically significant were
assessed in 982 patients who have been treated in trial 1 and trial 2 in 21 trials ranging in dosage
while administering the drug in 0.1 towards 20 mg/kg doses.
3. Should explain the type of drug you might develop,
Two drugs can be developed using the POPDC1 protein such as Ipilimumab (Yervoy) for
treating melanoma cancer and Brentuximab vedotin or adcetris for treating lymphoma cancer.
The first one is a dermatology drug while the second one is for hematology usage. The drugs act
as human antibody drug conjugate. The evidence supports the fact that POPDC1 can be applied
therapeutically to treat various cancers.
4. what about side effects

POPDC1 AS THERAPEUTIC TARGET FOR CANCER 3
Each of these drugs can lead to fatal and severe adverse reactions that are immune-
mediated. Such reactions may be on any organ system but the most probable adverse effects
include hepatitis, enterocolitis, neuropathy, endocrinopathy and dermatitis or toxic epidermal
necrolysis. These reactions are normally noted during cancer treatment but minority outcomes
are experienced some weeks or months after the drug discontinuation.
5. What the likely effect would be
Its presence discourages the development of a phenotype in breast cancer that is
malignant by discouraging cell migration in the SKBR3, MDA231 and MCF7 cells. It also
prevents cell proliferation in SKBR3, MDA231 cells that are highly aggressive. At the same
time, POPDC1 overexpression reverses the malignant phenotype cells to be less active through
significant inhibition of cell proliferation and migration in the cells of breast cancer. Data from
other studies also shows that absence of the POPDC1 encourages cell invasion and migration in
hepatocellular carcinoma, glioblastoma, colorectal and gastric cancers but also support the
POPDC1 therapeutic function in breast cancer.
6. Then you want to explain the next steps that are required to achieve this
For metastatic or unresectable melanoma, the dosage recommended is 3 mg/kg that
should be intravenously administered over 90 minutes after every three weeks leading to a
maximum of four doses. In case toxicity is experienced, it is recommended to delay dosage
though all the treatment need to be administered in a time period of 16 weeks for first dosage.
For adjuvant melanoma treatment, the recommended dosage is 10mg/kg that should be
intravenously administered over 90 minutes after every three weeks leading to a maximum of
four doses. This dosage is followed by other 10mg/kg in 12 weeks leading up to 3 years. When
toxicity is experienced one is recommended to omit the doses instead of delaying.

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7. Where it would target (Popeye domain) and why
This condition is achieved after the cAMP binds with the Popeye domain which then
establishes a protein function in the cells plasma membrane. The Popeye domain is the one that
carries the POPDC1 protein that have a high affinity of bonding the cAMP effector protein
molecules. The condition then creates a good environment for the POPDC1 availability.
8. Where are the gaps in the research?
However, the mechanism through which the POPDC1 controls cell proliferation and
migration in breast, gastric, colorectal, hepatocellular carcinoma, and glioblastoma cancers needs
to have a clear elucidation that permits directed therapeutic development using POPDC1 and the
role of its entire molecule. Future researches need to give this clarity.