scholarly journals Antibody-Based Immunotoxins for Colorectal Cancer Therapy

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1729
Author(s):  
Laura Sanz ◽  
Raquel Ibáñez-Pérez ◽  
Patricia Guerrero-Ochoa ◽  
Javier Lacadena ◽  
Alberto Anel
Keyword(s):  
Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Therapeutic Potential ◽  
Treatment Options ◽  
Clinical Activity ◽  
Comprehensive Overview ◽  
Ongoing Research ◽  
Promising Strategy ◽  
Selection Of ◽  
Target Cancer

Monoclonal antibodies (mAbs) are included among the treatment options for advanced colorectal cancer (CRC). However, while these mAbs effectively target cancer cells, they may have limited clinical activity. A strategy to improve their therapeutic potential is arming them with a toxic payload. Immunotoxins (ITX) combining the cell-killing ability of a toxin with the specificity of a mAb constitute a promising strategy for CRC therapy. However, several important challenges in optimizing ITX remain, including suboptimal pharmacokinetics and especially the immunogenicity of the toxin moiety. Nonetheless, ongoing research is working to solve these limitations and expand CRC patients’ therapeutic armory. In this review, we provide a comprehensive overview of targets and toxins employed in the design of ITX for CRC and highlight a wide selection of ITX tested in CRC patients as well as preclinical candidates.

scholarly journals Metformin and Niclosamide Synergistically Suppress Wnt and YAP in APC-Mutated Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3437
Author(s):  
Hee Eun Kang ◽  
Yoojeong Seo ◽  
Jun Seop Yun ◽  
Sang Hyun Song ◽  
Dawool Han ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Therapeutic Strategy ◽  
Target Gene ◽  
Advanced Colorectal Cancer ◽  
Therapeutic Potential ◽  
Cancer Stemness ◽  
Reciprocal Regulation ◽  
Canonical Wnt

The Wnt and Hippo pathways are tightly coordinated and understanding their reciprocal regulation may provide a novel therapeutic strategy for cancer. Anti-helminthic niclosamide is an effective inhibitor of Wnt and is now in a phase II trial for advanced colorectal cancer (CRC) patients. We found that Axin2, an authentic target gene of canonical Wnt, acts as aYAP phosphorylation activator in APC-mutated CRC. While niclosamide effectively suppresses Wnt, it also inhibits Hippo, limiting its therapeutic potential for CRC. To overcome this limitation, we utilized metformin, a clinically available AMPK activator. This combinatory approach not only suppresses canonical Wnt activity, but also inhibits YAP activity in CRC cancer cells and in patient-derived cancer organoid through the suppression of cancer stemness. Further, combinatory oral administration suppressed in vivo tumorigenesis and the cancer progression of APC-MIN mice models. Our observations provide not only a reciprocal link between Wnt and Hippo, but also clinically available novel therapeutics that are able to target Wnt and YAP in APC-mutated CRC.

scholarly journals Natural Compounds in Sex Hormone-Dependent Cancers: The Role of Triterpenes as Therapeutic Agents

2021 ◽  
Vol 11 ◽  
Author(s):  
Codruţa Şoica ◽  
Mirela Voicu ◽  
Roxana Ghiulai ◽  
Cristina Dehelean ◽  
Roxana Racoviceanu ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Treatment Options ◽  
Active Role ◽  
Structural Features ◽  
Sex Hormone ◽  
Ongoing Research ◽  
New Treatment ◽  
Highly Correlated

Sex hormone-dependent cancers currently contribute to the high number of cancer-related deaths worldwide. The study and elucidation of the molecular mechanisms underlying the progression of these tumors was a double-edged sword, leading to the expansion and development of new treatment options, with the cost of triggering more aggressive, therapy resistant relapses. The interaction of androgen, estrogen and progesterone hormones with specific receptors (AR, ER, PR) has emerged as a key player in the development and progression of breast, ovarian, prostate and endometrium cancers. Sex hormone-dependent cancers share a common and rather unique carcinogenesis mechanism involving the active role of endogenous and exogenous sex hormones to maintain high mitotic rates and increased cell proliferation thus increasing the probability of aberrant gene occurrence and accumulation highly correlated with abnormal cell division and the occurrence of malignant phenotypes. Cancer related hormone therapy has evolved, currently being associated with the blockade of other signaling pathways often associated with carcinogenesis and tumor progression in cancers, with promising results. However, despite the established developments, there are still several shortcomings to be addressed. Triterpenes are natural occurring secondary metabolites biosynthesized by various pathways starting from squalene cyclization. Due to their versatile therapeutic potential, including the extensively researched antiproliferative effect, these compounds are most definitely a cornerstone in the research and development of new natural/semisynthetic anticancer therapies. The present work thoroughly describes the ongoing research related to the antitumor activity of triterpenes in sex hormone-dependent cancers. Also, the current review highlights both the biological activity of various triterpenoid compounds and their featured mechanisms of action correlated with important chemical structural features.

Supporting Treatment Decision Making in Advanced Cancer: A Randomized Trial of a Decision Aid for Patients With Advanced Colorectal Cancer Considering Chemotherapy

2011 ◽  
Vol 29 (15) ◽  
pp. 2077-2084 ◽  
Author(s):  
Natasha B. Leighl ◽  
Heather L. Shepherd ◽  
Phyllis N. Butow ◽  
Stephen J. Clarke ◽  
Margaret McJannett ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Decision Making ◽  
Randomized Trial ◽  
Advanced Cancer ◽  
Decision Aid ◽  
Advanced Colorectal Cancer ◽  
Treatment Options ◽  
Decisional Conflict ◽  
First Line ◽  
Line Chemotherapy

Purpose Decision making in advanced cancer is increasingly complex. We developed a decision aid (DA) for patients with advanced colorectal cancer who are considering first-line chemotherapy and reviewing treatment options, prognostic information, and toxicities. We examined its impact on patient understanding, treatment decisions, decisional conflict, decision making, consultation satisfaction, anxiety, and quality of life by using a randomized trial design. Patients and Methods In all, 207 patients with colorectal cancer who were considering first-line chemotherapy for metastatic disease were randomly assigned to receive a standard medical oncology consultation or a consultation in which the DA (take-home booklet with audio recording, reviewed by an oncologist) was used. Participants completed questionnaires postconsultation, postdecision, and 1 month later. Results In this study, 100 patients were randomly assigned to the control arm, and 107 received the DA. Median age of the sample was 62 years, 58% were male, 89% had a performance status of 0 or 1, and 36% had received prior adjuvant chemotherapy. Patients receiving the DA demonstrated a greater increase in understanding of prognosis, options, and benefits, with higher overall understanding (P < .001). Decisional conflict, treatment decisions, and achievement of involvement preferences were similar between the groups. Anxiety was similar across groups and decreased over time. Most patients were confident in a decision during the first consultation; 74% chose chemotherapy, 7% supportive care alone, and 10% observation. Conclusion This randomized trial of a decision aid in advanced cancer showed that its use in advanced colorectal cancer improved patient understanding of prognosis, treatment options, risks, and benefits without increasing anxiety. DAs can improve informed consent and can be tested through randomized trials even in the advanced cancer setting.

scholarly journals Nanovectors Design for Theranostic Applications in Colorectal Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-27 ◽  
Author(s):  
Riccardo Rampado ◽  
Sara Crotti ◽  
Paolo Caliceti ◽  
Salvatore Pucciarelli ◽  
Marco Agostini
Keyword(s):  
Colorectal Cancer ◽  
Systems Development ◽  
Comprehensive Overview ◽  
Body Of Knowledge ◽  
Biomedical Scientist ◽  
Novel Approaches ◽  
Theranostic Applications ◽  
Field Of Inquiry ◽  
Selection Of ◽  
Viability Evaluation

Colorectal cancer (CRC) is a diffused disease with limited therapeutic options, none of which are often curative. Based on the molecular markers and targets expressed by the affected tissues, numerous novel approaches have been developed to study and treat this disease. In particular, the field of nanotechnology offers an astonishingly wide array of innovative nanovectors with high versatility and adaptability for both diagnosis and therapy (the so called “theranostic platforms”). However, such complexity can make the selection of a specific nanocarrier model to study a perplexing endeavour for the biomedical scientist or clinician not familiar with this field of inquiry. This review offers a comprehensive overview of this wide body of knowledge, in order to outline the essential requirements for the clinical viability evaluation of a nanovector model in CRC. In particular, the differences among the foremost designs, their specific advantages, and technological caveats will be treated, never forgetting the ultimate endpoint for these systems development: the clinical practice.

scholarly journals Myricetin as a Promising Molecule for the Treatment of Post-Ischemic Brain Neurodegeneration

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 342
Author(s):  
Ryszard Pluta ◽  
Sławomir Januszewski ◽  
Stanisław J. Czuczwar
Keyword(s):  
Therapeutic Potential ◽  
Treatment Options ◽  
Dietary Therapy ◽  
Comprehensive Overview ◽  
Ischemic Brain ◽  
The Us ◽  
Potential Benefits ◽  
Anti Oxidant ◽  
Potential Clinical Utility ◽  
Pleiotropic Properties

The available drug therapy for post-ischemic neurodegeneration of the brain is symptomatic. This review provides an evaluation of possible dietary therapy for post-ischemic neurodegeneration with myricetin. The purpose of this review was to provide a comprehensive overview of what scientists have done regarding the benefits of myricetin in post-ischemic neurodegeneration. The data in this article contribute to a better understanding of the potential benefits of myricetin in the treatment of post-ischemic brain neurodegeneration, and inform physicians, scientists and patients, as well as their caregivers, about treatment options. Due to the pleiotropic properties of myricetin, including anti-amyloid, anti-phosphorylation of tau protein, anti-inflammatory, anti-oxidant and autophagous, as well as increasing acetylcholine, myricetin is a promising candidate for treatment after ischemia brain neurodegeneration with full-blown dementia. In this way, it may gain interest as a potential substance for the prophylaxis of the development of post-ischemic brain neurodegeneration. It is a safe substance, commercially available, inexpensive and registered as a pro-health product in the US and Europe. Taken together, the evidence available in the review on the therapeutic potential of myricetin provides helpful insight into the potential clinical utility of myricetin in treating neurodegenerative disorders with full-blown dementia. Therefore, myricetin may be a promising complementary agent in the future against the development of post-ischemic brain neurodegeneration. Indeed, there is a scientific rationale for the use of myricetin in the prevention and treatment of brain neurodegeneration caused by ischemia.

scholarly journals Treatment Options for Colorectal Cancer Liver Metastases

2020 ◽  
pp. 1-6
Author(s):  
Zhiming Zhao ◽  
Mengyang Li ◽  
Xianglong Tan ◽  
Zhiming Zhao
Keyword(s):  
Colorectal Cancer ◽  
Liver Transplantation ◽  
Liver Metastases ◽  
Immune Therapy ◽  
Treatment Options ◽  
Common Site ◽  
Colorectal Cancer Liver Metastases ◽  
Treatment Indications ◽  
Tremendous Progress ◽  
Selection Of

The liver is the most common site of metastasis in colorectal cancer (CRC). Treatment of liver metastases determines the prognosis of patients with CRC. Tremendous progress has been made during the last two decades, which has greatly improved the overall survival of CRC patients. Currently, various treatment options are available, including hepatectomy, liver transplantation, local regional therapy, chemotherapy, targeted therapy, and immune therapy, inevitably leading to some controversies on treatment indications and selection of treatment strategy. Here, we reviewed the existing approaches to treat colorectal cancer liver metastases, with the aim of examining several crucial questions regarding surgical resection, liver transplantation, and medical treatment in clinical practice.

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