Drug Discovery Today

Emerging role of deubiquitinases in modulating cancer chemoresistance

Ramipril, perindopril and trandolapril as potential chemosensitizers in ovarian cancer: Considerations for drug repurposing

Ovarian cancer (OC) has poor survival statistics and increasing prevalence. One of the new options for its therapy could be overcoming platinum resistance. In this review, we have considered the idea of repositioning angiotensin-converting enzyme inhibitors (ACE-Is) as chemosensitizers. These drugs have been shown to suppress angiogenesis and OC cell migration in preclinical studies. Moreover, clinical data have shown that using ACE-Is with standard chemotherapy prolongs patient survival. Based on this rationale, we discuss the available in vitro models of OC for future studies with ACE-Is and demonstrate an in silico approach that has enabled us to select the most promising molecules: perindopril, ramipril, trandolapril and their diketopiperazine derivatives.

PD-1/PD-L1 immune checkpoint blockade in ovarian cancer: Dilemmas and opportunities

Immune checkpoint inhibitors (ICIs) have revolutionized treatment in oncology. Antibodies against PD-1/PD-L1 and ICI-based combinations are under clinical investigations in multiple cancers, including ovarian cancer. However, the success of ICIs has not materialized in ovarian cancer, which remains one of the few malignancies where ICIs exhibit modest efficacy as either monotherapy or combination therapy. In this review, we summarize completed and ongoing clinical trials of PD-1/PD-L1 blockade in ovarian cancer, categorize the underlying mechanisms of resistance emergence, and introduce candidate approaches to rewire the tumor microenvironment (TME) to potentiate anti-PD-1/PD-L1 antibodies.

Metal-based approaches to fight cervical cancer

Cervical cancer (CC) is one of the leading causes of death among women worldwide. The current treatments for this cancer consist of invasive methods such as chemotherapeutic drugs, radiation, immunotherapy and surgery, which could lead to severe side effects and hinder the patient's life quality. Although metal-based therapies, including cisplatin and ruthenium-based compounds, offer promising alternatives, they lack specificity and harm healthy cells. Combining metal nanoparticles with standard approaches has demonstrated remarkable efficacy and safety in the fight against CC. Overall, this review is intended to show the latest advancements and insights into metal-based strategies, creating a promising path for more effective and safer treatments in the battle against CC.

Neoadjuvant chemotherapy-related platinum resistance in ovarian cancer

Neoadjuvant chemotherapy (NACT) has been regarded a standard treatment for advanced ovarian cancers for decades. Among patients who are poor candidates for primary debulking surgery (PDS), NACT is likely their only option in clinical practice. However, NACT failed to show any survival benefit in the reported randomized controlled trials (RCTs) and the meta-analyses, compared with PDS. This phenomenon raises concerns over the unfavorable influence of NACT, that is, the potential risk of inducing platinum resistance. In this review, we reveal the risk of NACT-related platinum resistance by summarizing the experimental and clinical evidence and discuss new attempts to avoid this phenomenon.