In a continuation of earlier in vitro studies, Plonowski et al. (pages 624–629) demonstrate, in this issue of the International Journal of Cancer, that vasoactive intestinal peptide (VIP) antagonists inhibit the growth of human androgen-independent prostate carcinomas in a mouse tumor model. Many advanced prostate cancer patients in remission eventually relapse with androgen-refractory disease, with limited remaining treatment options. The neuropeptide VIP and its receptors probably contribute to this progression by constituting an autocrine/paracrine mitogenic system. Hence, therapeutic agents blocking VIP receptors could potentially inhibit the proliferation of advanced, hormone-independent tumors. Sure enough, when Plonowski et al. treated nude mice carrying PC-3 human androgen-independent prostate carcinomas with VIP antagonists tumor size shrank by 62–67% compared to controls and the expression of mRNA for the oncogenes c-fos and c-jun declined by 34%. The effect of nonselective VIP/GH-RH antagonist JV-1-52 and specific VIP antagonist JV-1-53 on the growth of PC-3 tumor xenografts. Previous reports showed antiproliferative effects of neuropeptide growth hormone antagonists on lung, breast and pancreatic carcinomas. Now, prostate cancer joins the growing list of potential candidates for clinicial testing. Two reports introduce several new members of the growing family of cancer/testis (CT) antigens. Whereas de Wit et al. relied on high-density oligonucleotide array analysis (pages 547–553), Scanlan et al. mined the Unigene database for transcripts expressed exclusively in cancer and normal testis (pages 485–492). Cancer/testis antigens are expressed exclusively in developing germ cells of the testis and fetal ovary, the placental trophoblast and, most importantly, in many human cancers. The discovery that they can induce cytotoxic T lymphocyte responses in vitro and in vivo spurred widespread efforts to identify more potential target molecules for immunotherapeutic cancer vaccines. MMA-1A and its splice variant MMA-1B initially identified by de Wit et al. as malignant melanoma-associated antigens turned out to be expressed in testis and tumor samples of variable origin fitting the definition of CT antigens. Out of 1,325 original database hits, Scanlan et al. picked 73 candidates for further analysis. After investigating their tissue-specific mRNA expression pattern, three gene products qualified as bona fide CT genes. Expression of cancer/testis-associated Unigene database clusters in different normal adult tissues (a) and tumor cell lines (b). Both database mining and differential displays will be invaluable tools to identify more immunogenic tumor-associated antigens opening new perspectives for the development of polyvalent cancer vaccines. Unlike most other players on the cellular stage, bc10 makes itself conspicuous by its absence: this novel human bladder cancer-associated protein discovered by Gromova et al. is downregulated in invasive cancer (pages 539–546). It is difficult to predict the behavior of most bladder tumors based on conventional histopathological parameters, such as tumor grade and stage. Therefore, a great deal of effort is devoted to identify prognostic factors that could foretell the true malignant potential. A systematic search by the authors for biomarkers that correlate with a particular step of bladder cancer progression already yielded several candidates with bc10 being their latest discovery. Non-invasive human transitional cell carcinomas (TCCs), the most frequent subtype of bladder cancer, express this conserved, intronless gene but predictably lose bc10 expression when they develop into high-grade, invasive TCCs. The next challenge will be to figure out the significance of this carefully staged exit for bladder cancer progression. Expression of bc10 in non-invasive and invasive TCCs. Sustained high human papilloma virus (HPV) 16 loads in cervical scrapes confer an increased risk of progression from low-grade to high-grade cervical intraepithelial neoplasia (CIN II or III), report van Duin et al. (pages 590–595). Although infection with high-risk HPV types is strongly correlated with the development of cervical cancer in situ, most infections are transient. They either clear without giving rise to lesions or lead to spontaneously regressing, low-grade CINs. Van Duin et al. closely monitored viral counts in normal and abnormal cervical scrapes and established that the women with normal cervical smears and high HPV loads have a higher risk of developing a CIN lesion. Subsequently, a sustained or increased viral load indicates a greater chance of viral persistence and subsequent progression to a CIN II/III lesion. Further studies will be necessary to evaluate the merits of quantitative HPV testing in the clinical setting. Concept of HPV 16 load and progression of CIN lesions in women with normal and abnormal cytology.