Addressing the Right Targets in Oncology: Challenges and Alternative Approaches

Abstract

Translating existing and emerging knowledge of cancer biology into effective novel therapies remains a great challenge in drug discovery. A firm understanding of the target biology, confidence in the supporting preclinical research, and access to diverse chemical matter is required to lower attrition rates and prosecute targets effectively. Understanding past successes and failures will aid in refining this process to deliver further therapeutic benefit to patients. In this review, we suggest that early oncology drug discovery should focus on selection and prosecution of cancer targets with strong disease biology rather than on more chemically "druggable" targets with only modest disease-linkage. This approach offers higher potential benefit but also increases the need for innovative and alternative approaches. These include using different methods to validate novel targets and identify chemical matter, as well as raising the standards and our interpretation of the scientific literature. The combination of skills required for this emphasizes the need for broader early collaborations between academia and industry.

Patient-Derived Tumor Xenograft Models: Toward the Establishment of Precision Cancer Medicine

“…However, in the research and development of molecular targeted drugs, the results of non-clinical studies rarely predict clinical efficacy. This paradox is largely attributable to the lack of appropriate non-clinical models reflecting the diversity and complexity of tumors [17,18]. In other words, the existing DNA-damaging anti-cancer drugs are based on a relatively common and simple mechanism, namely the high proliferative activity of tumor cells.…”

Synthesis and Molecular Modelling Studies of New 1,3-Diaryl-5-Oxo-Proline Derivatives as Endothelin Receptor Ligands

“…Moreover, atrasentan has shown some adverse effects, such as fluid retention and an increased risk of hospitalization for heart failure [11]. Advancement in molecular biology has provided important techniques that play a pivotal role in the modern drug development process [12], allowing the discovery of several new drug targets, especially in oncology [13][14][15][16][17][18]. On the other hand, drug repurposing is becoming a more and more attractive approach among pharmaceutical companies due to the clear advantages in cost and time reduction compared to de novo drug development [19,20].…”