Progress in Drug Discovery & Biomedical Science

AdenoCure 3X: Establishing a Sensitized Cancer Cell Model to Accelerate Novel Drug Discovery

Ee Wern Tan — 2024-08-30

Cancer is a major cause mortality globally, and chemotherapy is frequently employed as a treatment for cancer. Regrettably, cancers possess the ability for developing resistance to conventional treatments, and the rising recurrence of these drug-resistant cancers requires further research and the advancement of treatment approaches. To address the growing challenge of chemoresistance, this study presents a novel approach for developing a sensitized cancer cell model using AdenoCure 3X to accelerate the discovery of novel drugs. We constructed a tetracistronic adenoviral vector, Ad-MBRG for targeted delivery of tumour suppressor genes MOAP-1, Bax, and RASSF1A, known to be epigenetically silenced in many cancers and contribute to apoptotic pathway dysfunction. This approach aims to restore apoptotic signaling and enhance cancer cell sensitivity to treatment. The study outlines a multi-step methodology for establishing the Ad-MBRG-mediated sensitized cell model, including amplification and quantification of Ad-MBRG particles, optimization of infection efficiency in the MCF7-CR cancer cell line, and evaluation of their sensitivity compared to non-infected controls. Furthermore, we explored the potential synergistic effects between Ad-MBRG infection and anti-cancer compounds derived from natural products. This model holds promise for screening anti-cancer compounds, particularly those from natural sources, and evaluating their potential to overcome chemoresistance. This paves the way for further exploration of adenovirus-mediated gene therapy as a platform for novel drug discovery and improved cancer treatment strategies.

Establishment of Adaptive Drug-resistant Colorectal Cancer Cell Model

Zhijack Fong — 2024-02-07

Colorectal cancer (CRC) ranks among the most prevalent cancers and contributes significantly to cancer-related fatalities. Chemoresistance in CRC poses a considerable therapeutic challenge, underscoring the need to comprehend the underlying mechanisms for the development of alternative strategies to overcome this resistance. Utilizing isogenic cell lines with acquired drug resistance is one of the prominent experiment approaches for studying chemoresistance, enabling the exploration of adaptive cellular responses to chemotherapeutic agents that confer resistance in cancers. However, establishing such cell models is challenging, and there are limited readily available protocols for scientists as references. This paper aims to elucidate the methodology for establishing a laboratory isogenic adaptive chemoresistant cell model, focusing on a cisplatin-resistant CRC cell model. From a panel of three human CRC cell lines, HCT116 was selected as the parent cell line due to its high cisplatin sensitivity. HCT116 cells were subjected to pulsed or continuous cisplatin treatments that resulted in successful selection of seventeen HCT116 sublines that exhibited varying degrees of cisplatin resistance. Only one HCT116 subline with transient acquired cisplatin resistance was established using pulsed exposure method while the method involved continuous cisplatin treatment has successfully established two resistant lines HCT116/I24781 and HCT116/I248 demonstrate 24.5-fold and 19.2-fold resistance respectively. These resistant cells showed significantly reduced growth rate with slight change in cell morphology and relatively stable resistance that remained unaffected for 8 continuous passages in cisplatin-free environment and 2 cryopreservation cycles. Together, these results suggest that continuous exposure with stepwise dose increase of drug is promising for establishing adaptive drug-resistant cell lines with significant drug resistance.

Pharmacological Management of Tuberculosis, Challenges, and Potential Strategies

Bernadette Xin Jie Tune — 2024-02-09

Tuberculosis (TB) is an infection caused by the pathogen Mycobacterium tuberculosis. The disease causes around 2 million deaths worldwide, and incidences of drug resistance only makes increases the number. The most vulnerable victims of TB infections are children and human immunodeficiency virus (HIV) patients. TB and HIV co-infections can be deadly in AIDS sufferers, as the immune system is not able to combat TB infections, hence worsening the infection. Common drugs to treat TB are available in the market, first-line drugs such as isoniazid and rifamycin are broad-spectrum drugs. Second-line antibiotics such as fluoroquinolones are also available. In this review, the mechanisms of action of TB drugs are briefly discussed, as wells as the respective resistant mechanisms of M. tuberculosis against these drugs. An updated treatment regime for TB management using bedaquiline, pretomanid and linezolid was also discussed, which shows 90% therapeutic efficacy against highly drug-resistant tuberculosis cases. Furthermore, novel strategies such as nanoparticle-conjugated TB drugs can improve drug delivery, TB drug efficiency while reducing side effects. However, importance on patient compliance to the treatment regime is still the most crucial part of TB management, hence initiatives can be put to improve patient awareness and education.

Nanomedicine in Oncology: A Critical Review on Epidemiology, Health Impacts, Challenges, and Future Outlook

Teh Coey — 2024-05-04

Cancer remains a leading public health issue globally due to its increasing morbidity rate, with cancer cases predicted to double over the next 20 years. While current conventional treatments are the primary go-to in treating cancers, they still present ineffective due to adverse side effects, poor targeting, and drug resistance. In recent years, nanomedicines have emerged as a better alternative for cancer treatment in maximizing drug delivery, bioavailability, and therapeutic efficacy through passive and active mechanisms. Despite having high potential, the poor clinical translations and recent fund retractions have led to limited progress in cancer nanomedicine. Thus, this review aims to review and identify the role of nanomedicine in oncology by analyzing the involved epidemiological populations, potential health impacts, possible outcomes, and current challenges in terms of economic, environmental, and ethical aspects. Further outlooks in improving nanomedicine therapeutic efficacy are also discussed, including switching approaches to nanomedicine development, modifying current regulatory guidelines, and providing training programs.