Patterns of Innate or Acquired Resistance to Anticancer Drugs: Our Experience to Overcome It
Paola Poma1, Manuela Labbozzetta1, Monica Notarbartolo2
1Pharmacology Unit, Department of Health Sciences and Mother and Child Care "G. D'Alessandro", University of Palermo; Department of Biological, Chemical and Pharmaceutical Science and Technology (STEBICEF), University of Palermo, Palermo, Italy.
Abstract:
Drug resistance, which is often of a multiple type, can be defined as the ability of cancer cells to obtain resistance to both conventional and novel chemotherapy agents. It remains a major problem to solve in cancer therapy. The mechanisms of resistance are multifactorial, and in our cellular models of acute myeloid leukemia, hepatocellular carcinoma, and triple-negative breast cancer, it involves the NF-κB pathway. In our opinion, multitarget molecules can be considered as privileged compounds capable of attacking and reversing the resistant phenotype. In the phenomena of both innate and acquired drug resistance that we have been studying since 1998 to today and up to 2016 under the guidance of Professor Natale D'Alessandro, more strictly pharmacological factors are certainly involved. These factors include P-glycoprotein and biological factors such as inhibitory proteins; apoptosis; the Raf-1 kinase inhibitor protein, an important tumor suppressor and metastasis inhibitor, which enhances drug-induced apoptosis of cancer cells; and Yin Yang, a transcription factor involved in drug resistance.
Insights
Cancer cells develop drug resistance through multifactorial mechanisms, including the NF-κB pathway. Multitarget molecules show promise in reversing this resistance, offering new therapeutic strategies for difficult-to-treat cancers.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Drug resistance in cancer is a significant clinical challenge, impacting treatment efficacy.
- Mechanisms of drug resistance are complex and multifactorial, involving various cellular pathways.
- The NF-κB pathway plays a crucial role in mediating drug resistance in cancer models.
Purpose of the Study:
- To investigate the role of the NF-κB pathway in drug resistance.
- To explore the potential of multitarget molecules in overcoming cancer drug resistance.
- To identify key biological and pharmacological factors contributing to drug resistance.
Main Methods:
- Utilized cellular models of acute myeloid leukemia, hepatocellular carcinoma, and triple-negative breast cancer.
- Analyzed the involvement of the NF-κB pathway in drug-resistant cancer cells.
- Examined pharmacological factors like P-glycoprotein and biological factors including apoptosis and specific proteins.
Main Results:
- The NF-κB pathway was identified as a key player in drug resistance across studied cancer types.
- Multitarget molecules are proposed as potential agents to reverse the resistant phenotype.
- Pharmacological factors (P-glycoprotein) and biological factors (apoptosis, Raf-1 kinase inhibitor protein, Yin Yang) are implicated in drug resistance.
Conclusions:
- The NF-κB pathway is a critical target for overcoming drug resistance.
- Multitargeting strategies hold promise for developing novel cancer therapies.
- Understanding the interplay of various factors is essential for effective cancer treatment.
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