Chemotherapy remains the preferred choice of treatment for prostate cancer but modest drug response and significant toxicity by conventional methods of administration limit their efficacy. In our study, we determined the efficacy of paclitaxel (Tx)‐loaded biodegradable nanoparticles (NPs) on tumor inhibition. We hypothesized that NPs following conjugation to transferrin (Tf) ligand (NPs‐Tf) would enhance the therapeutic efficacy of the encapsulated drug. The antiproliferative activity of NPs was determined in human prostate cancer cell line (PC3) and their effect on tumor inhibition in a murine model of prostate cancer. NPs (∼ 220 nm in diameter, 5.4% w/w drug loading) under in vitro conditions exhibited sustained release of the encapsulated drug (60% release in 60 days). The IC₅₀ (concentration of drug for 50% inhibition of cell growth) of the drug with Tf‐conjugated NPs (Tx‐NPs‐Tf) was about 5‐fold lower than that with unconjugated NPs (Tx‐NPs) or drug in solution. Animals that received a single‐dose intratumoral injection of Tx‐NPs‐Tf (Tx dose = 24 mg/kg) demonstrated complete tumor regression and greater survival rate than those that received either Tx‐NPs or Tx‐Cremophor® EL formulation. In conclusion, sustained release NPs demonstrated greater antitumor activity following their conjugation to Tf ligand.

Pancreatic cancer remains one of the most challenging malignancies to treat due to its late-stage diagnosis, aggressive progression, and high resistance to existing therapies. This review examines the latest advancements in early detection, and therapeutic strategies, with a focus on emerging biomarkers, tumor microenvironment (TME) modulation, and the integration of artificial intelligence (AI) in data analysis. We highlight promising biomarkers, including microRNAs (miRNAs) and circulating tumor DNA (ctDNA), that offer enhanced sensitivity and specificity for early-stage diagnosis when combined with multi-omics panels. A detailed analysis of the TME reveals how components such as cancer-associated fibroblasts (CAFs), immune cells, and the extracellular matrix (ECM) contribute to therapy resistance by creating immunosuppressive barriers. We also discuss therapeutic interventions that target these TME components, aiming to improve drug delivery and overcome immune evasion. Furthermore, AI-driven analyses are explored for their potential to interpret complex multi-omics data, enabling personalized treatment strategies and real-time monitoring of treatment response. We conclude by identifying key areas for future research, including the clinical validation of biomarkers, regulatory frameworks for AI applications, and equitable access to innovative therapies. This comprehensive approach underscores the need for integrated, personalized strategies to improve outcomes in pancreatic cancer.

Targeted molecular therapy has yielded remarkable outcomes in certain cancers, but specific therapeutic targets remain elusive for many others. As a result of two independent RNA interference (RNAi) screens, we identified pathway dependence on a member of the Janus-activated kinase (JAK) tyrosine kinase family, TYK2, and its downstream effector STAT1, in T-cell acute lymphoblastic leukemia (T-ALL). Gene knockdown experiments consistently showed TYK2 dependence in both T-ALL primary specimens and cell lines, and a small-molecule inhibitor of JAK activity induced T-ALL cell death. Activation of this TYK2–STAT1 pathway in T-ALL cell lines occurs by gain-of-function TYK2 mutations or activation of interleukin (IL)-10 receptor signaling, and this pathway mediates T-ALL cell survival through upregulation of the antiapoptotic protein BCL2. These findings indicate that in many T-ALL cases, the leukemic cells are dependent upon the TYK2–STAT1–BCL2 pathway for continued survival, supporting the development of molecular therapies targeting TYK2 and other components of this pathway. Significance: In recent years, “pathway dependence” has been revealed in specific types of human cancer, which can be important because they pinpoint proteins that are particularly vulnerable to antitumor-targeted inhibition (so-called Achilles' heel proteins). Here, we use RNAi technology to identify a novel oncogenic pathway that involves aberrant activation of the TYK2 tyrosine kinase and its downstream substrate, STAT1, which ultimately promotes T-ALL cell survival through the upregulation of BCL2 expression. Cancer Discov; 3(5); 564–77. ©2013 AACR. See related commentary by Fontan and Melnick, p. 494 This article is highlighted in the In This Issue feature, p. 471