Resistance to androgen deprivation therapy, or castration-resistant prostate cancer (CRPC), is often accompanied by metastasis and is currently the ultimate cause of prostate cancer-associated deaths in men. Recently, secondary hormonal therapies have led to an increase of neuroendocrine prostate cancer (NEPC), a highly aggressive variant of CRPC. Here, we identify that high levels of cell surface receptor Trop2 are predictive of recurrence of localized prostate cancer. Moreover, Trop2 is significantly elevated in CRPC and NEPC, drives prostate cancer growth, and induces neuroendocrine phenotype. Overexpression of Trop2 induces tumor growth and metastasis while loss of Trop2 suppresses these abilities in vivo. Trop2-driven NEPC displays a significant up-regulation of PARP1, and PARP inhibitors significantly delay tumor growth and metastatic colonization and reverse neuroendocrine features in Trop2-driven NEPC. Our findings establish Trop2 as a driver and therapeutic target for metastatic prostate cancer with neuroendocrine phenotype and suggest that high Trop2 levels could identify cancers that are sensitive to Trop2-targeting therapies and PARP1 inhibition.

Biohybrid microrobotics are exploited as a delivery approach to actively transport therapeutic payload to tumors. However, the therapeutic utility of this approach can be diminished by tumor hypoxia. Moreover, current biohybrid microrobotics design is mainly focused on the living organisms’ motility and biocompatibility, yet the unique biological function of the natural organism is often overlooked. Here, an all‐in‐one self‐propelled volvox‐based multifunctional robot, that is, Volbot, with built‐in capabilities of fluid mixing, multimode imaging, and photosynthesis‐mediated in situ oxygen generation that can potentially relieve hypoxia is developed. Volbots can follow a pre‐specified route and directionality under the control of a magnetic field. Red‐light irradiation (λ = 650 nm) can enhance the Volbot's locomotive behavior, enhance the mixing of biofluids, and modulate the oxygen production to improve the efficacy of photodynamic therapy. Moreover, Volbots can absorb near‐infrared irradiation and produce localized hyperthermia to treat tumors. Subcutaneous tumor suppression can be achieved by this high‐yield oxygen‐producing biohybrid “microfactory” in a photodynamic/photothermal‐synergistic therapy strategy. Furthermore, Volbots also offer imaging capabilities and exhibit considerable promise as a multifunctional microrobotics‐based theranostic approach for a precision tumor therapy strategy.

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Breast cancer remains the second most lethal cancer among women in the United States and triple-negative breast cancer is the most aggressive subtype with limited treatment options. Trop2, a cell membrane glycoprotein, is overexpressed in almost all epithelial cancers. In this study, we demonstrate that Trop2 is overexpressed in triple-negative breast cancer (TNBC), and downregulation of Trop2 delays TNBC cell and tumor growth supporting the oncogenic role of Trop2 in breast cancer. Through proteomic profiling, we discovered a metabolic signature comprised of TALDO1, GPI, LDHA, SHMT2, and ADK proteins that were downregulated in Trop2-depleted breast cancer tumors. The identified oncogene-mediated metabolic gene signature is significantly upregulated in TNBC patients across multiple RNA-expression clinical datasets. Our study further reveals that the metabolic gene signature reliably predicts poor survival of breast cancer patients with early stages of the disease. Taken together, our study identified a new five-gene metabolic signature as an accurate predictor of breast cancer outcome.

Highlights d SU086 inhibits prostate cancer growth in preclinical models of prostate cancer d SU086 targets heat shock protein 90 d SU086 alters prostate cancer glycolysis and decreases intratumoral metabolism d SU086 in combination with anti-androgens halts prostate cancer growth