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Tumor Discovery PPAR agonist and cancer

people will develop cancer; one in nine men and one in 12 limited number of cancers and can lead to unfavorable
women will die from the disease. The process of treating side effects, including cytokine release syndrome and a
cancer has always been intricate. Conventional therapeutic weakened immune response. Although immunotherapy
13
modalities, including radiotherapy, chemotherapy, and has been developed as an effective cancer treatment,
surgery, have been employed to treat cancer. 1 immunotherapy-based drugs often have poor outcomes
in solid tumors due to low infiltration of immune cells
The main treatments for cancer are surgery and
chemotherapy; however, patients frequently develop and decreased tumor immunogenicity, resulting in an
immunosuppressive tumor environment. Furthermore,
14
chemotherapeutic resistance within a few years after the lack of appropriate preclinical models for validating
starting treatment. Furthermore, side effects from distinct biomarkers, as well as inadequate methods for
2
chemotherapeutic drugs such as paclitaxel, carboplatin, tumor tissue collection, makes it more difficult to assess
and doxorubicin can significantly worsen quality of predictive biomarkers. 15
life. These side effects include weakness, itching, loss
of appetite, hair loss, and facial flushing, among others. Usually, hormonal treatments prevent steroid ligands
Consequently, novel therapeutic approaches and improved from attaching to the nuclear hormone receptor family,
predictive markers for chemotherapy, targeted therapies, which includes estrogen receptor and androgen receptor
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immunotherapy, and hormonal therapy are required. 3 (AR) in breast cancer and prostate cancer, respectively.
Various hormone receptors are expressed in cancer and
Advances in our understanding of the molecular mediate both growth stimulation and inhibition effects.
mechanisms underlying cancer progression have made it Hormones such as gonadotropin-releasing hormones,
possible to develop novel targeted therapies that are proving gonadotropins, androgens, estrogens, and progestins have
to be innovative and promising approaches for treating the been evaluated in several clinical trials to understand the
disease. As these therapies specifically target cancer cells mechanisms of tumorigenesis. 17-20 However, resistance
4
while avoiding harm to non-target cells, they are becoming is a common cause of failure in single-agent hormonal
increasingly significant. The strategies used in targeted therapy, and it is not the only factor at play. Therapies such
therapy include prodrugs, nanoparticulate antibody as leuprorelin and enzalutamide can lead to resistance
conjugates, small molecule inhibitors, and monoclonal through various mechanisms, including mutations in the
antibodies. However, recent studies have revealed that AR ligand-binding domain and the creation of variant AR
the presence of molecularly diverse tumors can lead proteins that can recognize antiandrogens (antagonists)
to treatment failures in several cases. Furthermore, as agonists. 21-23 In this comprehensive review, we have
5-8
although it was anticipated that targeted therapy would compiled the available research on the utilization of
cause fewer side effects than conventional chemotherapy, various peroxisome proliferator-activated receptor (PPAR)
significant toxicities are still observed. Trastuzumab, for agonists as a combination therapy with known cancer
example, has been linked to congestive heart failure as a modalities for different cancers.
known adverse effect. Common side effects of vascular
9
endothelial growth factor (VEGF) inhibitors and VEGF 2. Combination therapy for cancer
receptor inhibitors include hypertension, thromboembolic Considering the current situation, a synergistic approach
events, slowed wound healing, and an elevated risk of that combines a chemotherapeutic agent with another
bleeding, including tumor-related hemorrhage. 10
agent can be employed to target similar or different
By enhancing the immune response, immunotherapy genes for cancer treatment. Although the combination of
enables the patient’s immune system to destroy cancer cytotoxic drugs has garnered significant interest, concerns
cells. As a next-generation treatment for cancer, it has the remain regarding the potential risks of drug toxicity, cross-
potential to replace chemotherapy due to its effectiveness resistance, and compromised quality of life. Therefore,
24
against multiple tumors and its innovative therapeutic incorporating a biological agent alongside an established
properties. There are two types of immunotherapy: active chemotherapeutic drug presents a promising alternative to
11
and passive. Active immunotherapy includes chimeric optimize therapeutic outcomes while minimizing toxicity.
antigen receptor T cells, immunostimulatory vaccines, By targeting various molecular pathways implicated in
and genetically modified organisms that can recognize cancer development through diverse mechanisms of
specific cancer antigens. Passive immunotherapy, on action, combination therapy aims to enhance treatment
the other hand, involves using cytokines or checkpoint efficacy. 25,26 However, discovering novel therapeutic agents
inhibitors to indirectly enhance the patient’s immune is a complex and resource-intensive process that entails
response. Although these treatments are novel, clinical multiple steps, substantial time, and costs, including clinical
12
trial results indicate that they are only effective against a trials. Thus, drug repurposing offers several advantages
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Volume 3 Issue 4 (2024) 2 doi: 10.36922/td.4003