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Tumor Discovery A comprehensive review of bexarotene

may result in higher concentrations in tumor tissue, was used concomitantly with IFN α‐2b, the response rate
whereas oral administration allows for the distribution was similar to that reported for bexarotene used alone in
of bexarotene in both tumor and normal tissues, with the CTCL, with a response rate of 39% . Further explorations
[23]
potential for higher accumulation in tumors due to its are required to fully understand the usefulness of bexarotene
affinity for cancer cells. These variations in distribution as a single agent and a supportive therapy in CTCL.
impact the abundance of bexarotene across tumor versus
normal tissues [11,12] . 5.2. Lung cancer
Lung cancer is a malignant disease and remains the leading
5. Clinical applications of bexarotene in cause of cancer-related death for both men and women,
multiple disorders accounting for approximately 20% (1.6 million per year) of
Bexarotene is a newly discovered compound that total cancer death. Among the various types of lung cancer,
has proven to be an efficacious chemopreventive and non-small cell lung carcinoma (NSCLC) is the most
chemotherapeutic agent capable of treating a myriad of prevalent, representing almost 80% of all lung cancers.
diseases. Some of its uses are discussed below. Bexarotene has shown promise in the chemoprevention
against lung cancer in several mouse models. In a study
5.1. CTCL using an Rb1/p53 genetically engineered rat model to
treat small cell lung carcinoma, the combined treatment
CTCL is a group of non-Hodgkin’s lymphoma characterized of bexarotene and budesonide resulted in a significant
by the production of abnormal lymphocytes . It is a reduction in tumor incidence, number, and load with
[15]
lymphoproliferative T‐cell disorder resulting from the bexarotene . In addition, bexarotene was also assessed
[24]
initial migration of malignant T-lymphocytes . CTCL for its effects on 4-(methylnitrosoamino)-1-(3-pyridyl)-
[16]
is classified into two subtypes: Sézary syndrome (SS) and 1-butanol and vinyl carbamate-incited lung tumors in
mycosis fungoides (MF) . SS is a leukemic variation of female strain A mice. It has demonstrated high efficacy
[17]
CTCL that can be challenging to diagnose and treat . MF against both tamoxifen-resistant and tamoxifen-sensitive
[18]
is a well-known category of CTCL, characterized by the tumors in rodent models of human cancer, as well as in
multiplication of atypical epidermotropic cells/memory the rat N-nitrosomethylurea (NMU)-induced mammary
lymphocytes in the skin. The disease generally progresses carcinoma model. Furthermore, the combination therapy
over the years or even decades, transitioning from patches of bexarotene and paclitaxel exhibited synergism by
to plaques or tumors. inhibiting mammary tumors grown in the rat model .
[25]
In a research study, the safety, clinical tolerance, and Bexarotene was well tolerated when used in combination
pharmacokinetics of bexarotene were examined in patients with paclitaxel and carboplatin with no observed toxicity.
with late stages of cancer. The study observed anticancer Drug–drug interactions were also not observed between
2[9]
effects at a dose of 300 mg/m . Bexarotene induced bexarotene and the chemotherapy agents. Instead, a
apoptosis of malignant T cells, downregulated Th2 positive response to the treatment was observed in 25%
[26]
cytokines, and enhanced Th1 responses . A synergistic of the patients . In a non-randomized, open-label,
[19]
effect was observed when patients were administered Phase I clinical trial involving NSCLC, bexarotene was
bexarotene in combination with interferon (IFN)-α . studied in combination with gefitinib. The trial revealed
[20]
For the treatment of CTCL, bexarotene has shown that bexarotene reduced the C max and AUC 0 – 24 of gefitinib
promise when used along with psoralen plus ultraviolet through the induction of CYP3A4 by 40% and 44%,
[27]
A (PUVA) as salvage therapy leading to remission . respectively . Figure 3 depicts the synergistic effect of
[21]
A recent open-labeled clinical study focused on the effect bexarotene with other chemotherapeutic agents. Recently,
of concomitant treatment of bexarotene and PUVA was a study reported that bexarotene impedes the viability
conducted on Japanese CTCL patients. The combination of NSCLC cells, such as A549 cells and H1299 cells, by
was confirmed to be safe and markedly effective in increasing the activity of SLC10A2 (a protein-coding gene
[28]
treating CTCL; however, certain adverse effects, such as overexpressed on A549 cells and H1299 cells) .
hypertriglyceridemia, hypothyroidism, neutropenia, and The findings strongly encourage the relevance of
hypercholesterolemia, were reported . These adverse bexarotene as an adjuvant drug in combination with other
[22]
effects can be easily managed with monitoring and chemotherapeutic agents for the treatment of NSCLC.
appropriate medication. The combined use of IFNs and
retinoids has shown immunomodulating effects and the 5.3. Breast cancer
potential to induce expressions of antiproliferative genes. Breast cancer is the most common type of cancer in women.
In a Phase Ⅱ clinical trial where 300 mg/m /day bexarotene Treating metastatic cancer is challenging, as merely 10 – 20%
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Volume 2 Issue 2 (2023) 4 https://doi.org/10.36922/td.0436