APR-246 Enhances Colorectal Cancer Sensitivity to Radiotherapy

Xie, Xuqin; Fan, Chuanwen; Luo, Bin; Zhang, Jing; Jensen, Lasse D.; Burman, Jonas; Jönsson, Carolin; Ljusberg, Anna; Larsson, Peter; Zhao, Zengren; Sun, Xiao‐Feng

doi:10.1158/1535-7163.mct-22-0275

Cited by 4 publications

(3 citation statements)

References 64 publications

(40 reference statements)

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“…There are several MDM2 inhibitors under study, such as RG7388/idasanutlin, a nutlin-3a derivative, HDM201, DS-3032b, AMG-232, BI 907828, APG-115, ALRN-6924, HDM201, etc that work alone or in combination with other chemo drugs or inhibitors against BCL-2/BCL-XL, MEK 1/2, PI3K, BCL-2/BCL-XL, BRAF, etc (Alaseem, 2023). APR-246 restores p53 activity in tumors bearing p53 mutants (Xie et al, 2023). Palbociclib is a CDK4/6 inhibitor that sensitizes cancer cells to mediated apoptosis mediated by TRAIL(J.…”

Section: Targeting P53mentioning

confidence: 99%

Apoptosis and Autophagy: Therapeutic Implications in Cancer

Halder

2024

IJERR

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Despite the advances in the medical field so far, cancer remains a global health priority even now. Considering the drug resistance and the failure of cancer therapies to achieve complete eradication of cancer cells in certain populations, developing molecules that induce programmed cell death or apoptosis has been the focus of cancer research for several decades. Apoptosis evasion is one of the hallmarks of cancer cells, and efforts continue to achieve complete annihilation of cancer cells through selective killing. On the other hand, autophagy, a mode of cell degradation, is considered a double-edged sword. Recent studies show that autophagy also can be manipulated to selectively target cancer cells based on the tumor microenvironment and cellular context. Studies show that autophagy is an evolutionarily conserved process initiated during stress response and has enormous importance in maintaining physiological balance. Most importantly, the dynamic equilibrium between apoptosis and autophagy is crucial in maintaining cellular homeostasis. Although a ‘cell eating’ process, the fate of autophagic cells depends entirely on the nature of stress and the extent of crosstalk between autophagy. This understanding is of immense significance when designing therapeutic interventions targeting apoptosis and autophagy. Currently, several studies are ongoing to gain insights into the role of autophagy in cancer initiation, invasion, progression, angiogenesis, and metastasis. This review focuses on the two major cell death mechanisms, apoptosis and autophagy, in the context of cancer, their crosstalk, and the therapeutic interventions targeting both modes of cell death.

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Section: Targeting P53mentioning

confidence: 99%

Apoptosis and Autophagy: Therapeutic Implications in Cancer

Halder

2024

IJERR

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“…Strategies that have been used to target mut-p53 include stabilization of wt-p53, restoration of DNAbinding capacity to mut-p53, refolding, prevention of mut-p53 misfolding, and promoting the expression of full length wt-p53 from mRNAs with the nonsense mutation [82]. An example of an active clinical trial drug that can rescue mut-p53 and restore its tumorsuppressor function is the small molecule eprenetapopt (APR-246) [111]. The role of this drug was investigated in pancreatic cancer cell lines.…”

Section: Targeting Mutant P53mentioning

confidence: 99%

Driver Mutations in Pancreatic Cancer and Opportunities for Targeted Therapy

Olaoba,

Adelusi,

Yang

et al. 2024

Cancers

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Pancreatic cancer is the sixth leading cause of cancer-related mortality globally. As the most common form of pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC) represents up to 95% of all pancreatic cancer cases, accounting for more than 300,000 deaths annually. Due to the lack of early diagnoses and the high refractory response to the currently available treatments, PDAC has a very poor prognosis, with a 5-year overall survival rate of less than 10%. Targeted therapy and immunotherapy are highly effective and have been used for the treatment of many types of cancer; however, they offer limited benefits in pancreatic cancer patients due to tumor-intrinsic and extrinsic factors that culminate in drug resistance. The identification of key factors responsible for PDAC growth and resistance to different treatments is highly valuable in developing new effective therapeutic strategies. In this review, we discuss some molecules which promote PDAC initiation and progression, and their potential as targets for PDAC treatment. We also evaluate the challenges associated with patient outcomes in clinical trials and implications for future research.

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“…Colorectal cancer (CRC), featured by aggressive metastasis, recurrence, and poor prognosis, is among the most prevalent and deadly diseases globally. , Current clinical treatments of CRC, including surgery, chemotherapy, , and radiotherapy, are severely limited because of their ineffectiveness, low specificity, and unsatisfactory time/spatial controllability. Therefore, developing precise diagnostic methods and low-damage therapeutic approaches is a crucial step in reducing the mortality rates associated with CRC.…”

mentioning

confidence: 99%

Synergistically Enhanced Chemodynamic Therapy Induced by NIR-II Photothermal Therapy with MRI/CT Imaging Guidance for Colorectal Cancer

Liu,

Hong,

Pan

et al. 2024

ACS Materials Lett.

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Chemodynamic therapy (CDT) exhibits unsatisfactory therapeutic efficacy for colorectal cancer (CRC) due to the hyposensitive Fenton reaction. Herein, we constructed a novel multifunctional nanoplatform based on bismuth-doped iron selenide nanoparticles (BFS NPs) for promoting the therapeutic performance of CDT on CRC. BFS NPs can realize CDT and second near-infrared photothermal therapy (NIR-II PTT) by means of the Fenton reaction and an excellent photothermal conversion efficiency (η = 31.9%). Moreover, the rising temperature induced by NIR irradiation accelerates the Fenton reaction rate because of there being more activated H 2 O 2 , thereby improving reactive oxygen species (ROS) levels to address the insufficient hydrogen peroxide concentration. The results showed that the combination of CDT with NIR-II PTT significantly inhibits the growth of CRC and minimizes adverse reactions. Meanwhile, bismuth doping endows the BFS NPs with superior CT imaging and T 2 -weighted magnetic resonance imaging (T 2 -MRI) capacities. These unique properties offer an appropriate treatment time window for guiding NIR-II PTT. In summary, this nanoplatform improves the therapeutic effect of CDT and accurately regulates NIR-II PTT by MRI/ CT imaging guidance, which provides a new perspective for effective and precise therapy of CRC.

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APR-246 Enhances Colorectal Cancer Sensitivity to Radiotherapy

Cited by 4 publications

References 64 publications

Apoptosis and Autophagy: Therapeutic Implications in Cancer

Apoptosis and Autophagy: Therapeutic Implications in Cancer

Driver Mutations in Pancreatic Cancer and Opportunities for Targeted Therapy

Synergistically Enhanced Chemodynamic Therapy Induced by NIR-II Photothermal Therapy with MRI/CT Imaging Guidance for Colorectal Cancer

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