Legitimate Target Research Articles

The Just War Tradition: Translating the Ethics of Human Dignity into Political Practices

This essay argues that the ambiguities of the just war tradition, sifted through a feminist critique, provides the best framework currently available for translating the ethical entitlement to human dignity into concrete feminist political practices. It offers a gendered critique of war that pursues the just war distinction between legitimate and illegitimate targets of wartime violence and provides a gendered analysis of the peace which the just war tradition obliges us to preserve and pursue.

Long-term course of bipolar I and II disorders: chronicity, dimensionality and relapse

Studies of the longitudinal natural history of the longterm course of illness (up to 20 years) of patients with bipolar I (BP-I) and bipolar II (BP-II) have found that both disorders are highly chronic. BP-l patients were symptomatic from their illness only 47% of the weeks and BP-II patients were symptomatic 54% of the weeks. All levels of depressive and manic symptom severity ranging from the subsyndromal to syndromal level fluctuated frequently within the same bipolar patient over time, indicating that both BP-I and BP-II disorders are symptomatically expressed across time as dimensional illnesses. Minor and subsyndromal manic and depressive symptoms were 3 times more common than syndromal level symptoms of mania and major depression. Depressive symptoms were three times more common than manic during the course of BP-I patients, and BP-II is overwhelmingly a depressive illness in which depressive symptoms are over 30 times more common than symptoms in the manic spectrum. Examination of hypomanic episodes in BP-II revealed that hypomanias of short duration (2-6 days) compared to long duration (more than 6 days) are not clinically significantly different and appear to be part of the same disease process. Detailed analyses of psychosocial impairment during the course of bipolar illness show that affective symptom severity and psychosocial disability increase and decrease in parallel. Depressive symptoms are equally disabling in BP-I and BP-II, often more disabling than manic/hypomanic symptoms. When asymptomatic, BP-I and BP-II patients' psychosocial function normalizes and no disability is present. Recovery from episodes in BP-I and BP-II with ongoing residual subsyndromal affective symptoms is associated with risk for very rapid relapse. Thus, all levels of affective symptom severity, including subsyndromal, are legitimate targets for therapeutic intervention to reduce risk of relapse and disability. The predominance of depressive symptoms indicates that more emphasis should be placed on the identification and management of depressive symptoms that present in patients with bipolar I and II disorders.

Pronatalism, Eugenics, and the Politics of State Health in Weimar Germany

During the Weimar Republic years, the public sphere gobbled up a great deal of previously private territory. Decisions that had been matters of religious doctrine and intra-familial economics became subjects of loud, vigorous, and public debate. Family size decreased, the birthrate dropped, and popular wisdom proposed that women were to blame. Women's choices regarding marriage, childbearing, birth control, work, style, and personal habits were considered legitimate targets of public intervention. Childbearing, particularly, became the conceptual nexus of multiple social and moral concerns. Highly charged arguments about motherhood and the declining birthrate emblematized deep anxieties: many people feared liberalization of sexual behavior and morality, and struggled to re-envision women's roles amid the tumult of rapid industrialization and economic upheaval. Against a backdrop of accelerating modernization, the pronatalist movement was born, from complex factors and comprised of unlikely allies, with the stated aim of increasing population and elevating the status of motherhood.I will argue that, far from being an exclusively right-wing or anti-feminist phenomenon, pronatalism was expressed across the political spectrum. While the declining birth rate provided a focal point for the energies of the pronatalist movement, its efforts were deeply entwined with subtler ideological elements, such as the construction of womanhood and modernizing identity. Pronatalist policy debates were exploited by female activists on the left and right as one of the few areas where their political activity could be effective. In matters of motherhood, if nowhere else, women seemed to possess natural expertise and innate moral superiority, and they used the privileging of their perspectives to claim authority in the public arena.

Review: Postprandial glycaemia and cardiovascular risk

Cardiovascular disease (CVD) accounts for almost 75% of mortality in subjects with type 2 diabetes. There is emerging evidence (epidemiological and There is emerging evidence (epidemiological and experimental studies) that postprandial glucose (PPG) contributes significantly to CVD risk, although to date there are no large scale interventional studies with the primary objective of reducing cardiovascular complications by targeting PPG. There is still continuing debate about the definition of postprandial hyperglycaemia. Moreover, we now know more of the cellular mechanisms being triggered in response to glucose excursions which may offer an explanation to this increased susceptibility to CVD. The contribution of PPG to glycosylated haemoglobin, is predominant in relatively well controlled subjects with type 2 diabetes. Hence, PPG is emerging as a legitimate therapeutic target to minimise CVD risk. This review looks at the evidence linking postprandial hyperglycaemia to CVD, the cellular mechanisms explaining this enhanced risk and a therapeutic strategy to address PPG.

Protein kinase C isozymes as therapeutic targets for treatment of human cancers

Summary PKC isozymes play specific, non-redundant functional roles in numerous cellular processes,including proliferation, differentiation, cellular invasion and apoptosis. We have determinedthat PKCβII and PKCι are both critical pro-carcinogenic genes involved in multiple humancancers. PKCι is a bonafide human oncogene, the first PKC isozyme that can be so classified.Both PKCβII and PKCι are legitimate therapeutic targets to which novel targeted therapy hasbeen successfully developed and is being evaluated clinically. Acknowledgements We would like to thank all the members of the Fields laboratory for their contributions to the work described in thisreview. We would also like to acknowledge the work of the many investigators whose combined work has madecritical contributions to our understanding of PKC functions in cancer. Space limitations necessitated a relativelynarrow focus in this review. We apologize to colleagues whose contributions were not cited due to these constraints.The work described here was supported by grants from the National Cancer Institute to APF (R01 CA081436 andR01CA056869), and to NRM (R01CA094122). Additional funding was provided by the American Lung Association/LUNGevity Lung Cancer Discovery Award (LCD-22766-N), the James and Esther King Biomedical ResearchProgram, and the V Foundation for Cancer Research to APF.

'Targeted Killings': Problems with the Approach of the Israeli High Court of Justice

A petition challenging the legality of the Israeli practice of assassinating suspected terrorists was brought before the Israeli High Court of Justice n January 2002. In February 2005, the Israeli Prime Minister announced a suspension of the policy, and as such the proceedings were stayed. The policy was reinitiated in June of 2005. As a consequence, additional hearings were held in December 2005. What this article argues is first, the interpretation of International Law offered by Chief Justice Barak casts the net too wide when interpreting the circumstances when civilians can be legitimate targets in armed conflicts; and second, given the modalities of the way in which the policy is implemented, the limitations recognised by the Court cannot be enforced and will not have any meaningful effect.

Targeting the oncogenic protein kinase Cι signalling pathway for the treatment of cancer

PKC (protein kinase C) isoenzymes are key signalling components involved in the regulation of normal cell proliferation, differentiation, polarity and survival. The aberrant regulation of PKC isoenzymes has been implicated in the development of many human diseases including cancer [Fields and Gustafson (2003) Methods Mol. Biol. 233, 519-537]. To date, however, only one PKC isoenzyme, the aPKC [atypical PKCiota (protein kinase Ciota)], has been identified as a human oncogene [Regala, Weems, Jamieson, Khoor, Edell, Lohse and Fields (2005) Cancer Res. 65, 8905-8911]. PKCiota has also proven to be a useful prognostic marker and legitimate target for the development of novel pharmacological agents for the treatment of cancer. The PKCiota gene resides at chromosome 3q26 and is a frequent target of tumour-specific gene amplification in multiple forms of human cancer. PKCiota gene amplification in turn drives PKCiota overexpression in these cancers. Genetic disruption of PKCiota expression blocks multiple aspects of the transformed phenotype of human cancer cells including transformed growth in soft agar, invasion through Matrigel and growth of subcutaneous tumours in nude mice. Genetic dissection of oncogenic PKCiota signalling mechanisms demonstrates that PKCiota drives transformed growth by activating a PKCiota --> Rac1 --> PAK (p21-activated kinase) --> MEK [MAPK (mitogen-activated protein kinase) 1,2/ERK (extracellular-signal-regulated kinase) kinase] 1,2 signalling pathway [Regala, Weems, Jamieson, Copland, Thompson and Fields (2005) J. Biol. Chem. 280, 31109-31115]. The transforming activity of PKCiota requires the N-terminal PB1 (Phox-Bem1) domain of PKCiota, which serves to couple PKCiota with downstream effector molecules. Hence, there exists a strong rationale for developing novel cancer therapeutics that target the PB1 domain of PKCiota and thereby disrupt its interactions with effector molecules. Using a novel high-throughput drug screen, we identified compounds that can disrupt PB1-PB1 domain interactions between PKCiota and the adaptor molecule Par6 [Stallings-Mann, Jamieson, Regala, Weems, Murray and Fields (2006) Cancer Res. 66, 1767-1774]. Our screen identified the gold compounds ATG (aurothioglucose) and ATM (aurothiomalate) as specific inhibitors of the PB1-PB1 domain interaction between PKCiota and Par6 that exhibit anti-tumour activity against NSCLC (non-small-cell lung cancer) both in vitro and in vivo. Structural analysis, site-directed mutagenesis and modelling indicate that ATM specifically targets the PB1 domain of PKCiota to mediate its anti-tumour activity [Erdogan, Lamark, Stallings-Mann, Lee, Pellechia, Thompson, Johansen and Fields (2006) J. Biol. Chem. 281, 28450-28459]. Taken together, our recent work demonstrates that PKCiota signalling is required for transformed growth of human tumours and is an attractive target for development of mechanism-based cancer therapies. ATM is currently in Phase I clinical trials for the treatment of NSCLC.

A Phase II Trial of Bortezomib and Prednisone for Castration Resistant Metastatic Prostate Cancer

We defined the antitumor effects of bortezomib alone and in combination with prednisone in patients with progressive, castration resistant metastatic prostate cancer. A total of 30 men with progressive castration resistant disease were treated in 2 groups. Cohort 1 received 1.5 mg/m2 bortezomib intravenously twice weekly for 2 cycles (2 weeks on and 1 week off), followed by 1.6 mg/m2 weekly (4 weeks on and 2 weeks off). Prednisone (10 mg) was given orally throughout. Cohort 2 comprised patients with limited chemotherapy exposure who received a decreased dose of bortezomib (1.3 mg/m2) during the induction period with prednisone added only at disease progression. The primary end point was no evidence of disease progression at 12 weeks, defined as no increase in prostate specific antigen from baseline and no radiographic progression. Interleukin-6 was assessed to correlate with antitumor effects. One of 24 evaluable patients (4%) achieved the primary end point. In cohort 1, 18 patients were treated, 13 were evaluable for response and 4 discontinued treatment due to toxicities, including 3 before attaining the point of being evaluable. No patient achieved the primary end point. In cohort 2, 12 patients were treated and 11 were evaluable for response. Toxicity was slightly mitigated compared with that in cohort 1. One patient achieved the primary end point. Interleukin-6 did not correlate with posttreatment prostate specific antigen changes in either cohort. Although interleukin-6 and other pathways regulated by nuclear factor-kappa B may be legitimate targets, treatment with bortezomib alone and with prednisone does not appear to have significant antitumor effects in patients with castration resistant metastatic prostate cancer.

Proteomics Evaluation of Chemically Cleavable Activity-based Probes

Activity-based probes (ABPs) that specifically target subsets of related enzymatic proteins are finding increasing use in proteomics research. One of the main applications for these reagents is affinity isolation of probe-labeled targets. However, the use of cheap and efficient biotin affinity tags on ABPs can be problematic due to difficulty in release of captured proteins. Here we describe the evaluation of activity-based probes carrying a chemically cleavable linker that allows selective release of probe-labeled proteins under mild elution conditions that are compatible with mass spectrometric analysis. Specifically, we compare results from standard on-bead digestion of probe-labeled targets after affinity purification with the results obtained using chemoselective cleavage. Results are presented for multiple APBs that target both serine and cysteine proteases. These results highlight significant improvements in the quality of data obtained by using the cleavable linker system.

The Civil Nuclear Constabulary: Accountability and Policing Post 9/11

Britain now appears to be a legitimate target for terrorists who may use a variety of tactics and devices to cause as many casualties, disruption and as much panic in society as possible. One way to achieve this would be through the acquisition of nuclear or biological material in order to create a ‘dirty’ weapon. The organisation responsible for guarding civil nuclear sites is a recently formed police agency called the Civil Nuclear Constabulary. The CNC is an armed police force which is the first response for any attempt to unlawfully obtain or tamper with nuclear material. This article raises the question of whether the CNC can be considered as a police organisation and raises some anomalies regarding the accountability and governance of such a vital organisation.

Influencer and other “buying” roles in the decision‐making process of retirement housing purchasers

PurposeThe purpose of this paper is to show that the role of children in persuading their parents to move is known to be significant, but there has been extensive debate about the roles of other people involved in the process. It is necessary to investigate who plays these roles, for they will be legitimate targets for informative promotion or help from not‐for‐profit agencies – the public sector and voluntary/charitable organisations – wanting to improve the older person's decision making when choosing from a range of housing options.Design/methodology/approachThe paper shows that questionnaires were delivered to every property in nine retirement housing schemes, chosen at random, in the West Midlands region of the UK. Approximately 200 were completed. Semi‐structured interviews were undertaken with 20 of the respondents.FindingsThe findings in this paper demonstrate that almost all initiators were from within the family. The spouse and adult children were the most important influencers, but children had the greatest impact because almost all respondents had children, whereas only a quarter were married. Respondents alone made the decision to purchase in three‐quarters of instances.Originality/valueThe paper shows that not‐for‐profit agencies, when providing information and offering advice about retirement housing, need to target the potential purchaser, the spouse, adult children and other relatives. Other influencers can almost be ignored. Such action will improve the decision‐making process.

Hostile Environment of the Gastroesophageal Junction

The gastroesophageal junction is remarkable for its high prevalence of mucosal pathology including inflammation, erosions, metaplasia, and adenocarcinoma. The incidence of disease focused at this site has increased in the West over recent decades and this has coincided with a decline in Helicobacter pylori infection and atrophic gastritis. This is consistent with most disease at the gastroesophageal junction being due to damage by refluxing acidic gastric juice. Several observations may explain the focusing of mucosa pathology at the gastroesophageal junction. Recent studies have demonstrated much greater acid exposure of the esophageal squamous mucosa near to the gastroesophageal junction than at 7-cm proximal to this where acid reflux has been traditionally measured. The mechanism of this short segment reflux is unclear but it is likely to be relevant to the high incidence of pathology affecting the most distal esophagus and in asymptomatic subjects. In addition, it has been recognized that the proximal cardia region of the stomach largely escapes the buffering effect of food and remains highly acidic after meals. This unbuffered acid pocket will be available for refluxing into the esophagus during the postprandial reflux when transient lower esophageal relaxations are most frequent. The gastroesophageal junction is also where saliva meets acidic gastric juice and this results in very active and potentially mutagenic luminal nitrosative chemistry. This arises from the reaction between the high concentrations of nitrite in saliva and the hydrochloric acid and ascorbic acid in gastric juice. The gastroesophageal junction is thus a site of very active chemical warfare, the primary function of which is to destroy potentially pathogenic ingested microorganisms. However, as with all legitimate targets, there is always a risk of collateral damage.

New Developments in Diketo-Containing Inhibitors of HIV-1 Integrase

HIV-1 integrase is one of the three enzymes, which are critical for viral replication. It catalyzes the integration of the HIV genome into the cellular chromosome. Since there is no known human homolog to integrase, its inhibition is one of the most promising novel drug targets for anti-retroviral therapy with potential advantage over existing therapies. To date, numerous compounds with diverse structural features have been reported as integrase inhibitors, among which the diketo-containing inhibitors of HIV-1 integrase represent a major lead for anti-HIV drug development. The discovery of diketo acids plays an important role in validating integrase as a legitimate target for treatment of AIDS. In this review, we summarize several drug candidates in clinical trials and new diketo-containing inhibitors of HIV-1 integrase discovered recently.

A CERTain Role for Ceramide in Taxane-Induced Cell Death

An unexpected benefit of functional genomic screens is that at times they answer questions that they were not designed to ask. A siRNA screen reported by Swanton et al. in this issue of Cancer Cell reveals that silencing of spindle assembly checkpoint genes facilitates mitotic slippage, resulting in escape from taxane-induced cell death, aneuploidy, and chromosomal instability, hallmarks of taxane resistance. Unexpectedly, the screen disclosed that the sphingolipid ceramide is a key regulator of the taxane-mediated spindle assembly checkpoint and taxane-induced cell death. Ceramide metabolism thus serves as a legitimate target for modulation of taxane effect on tumors.

The Question is When: The Ideology of Al Qaeda and the Reality of Bioterrorism

This article evaluates the threat of bioterrorism through a joint analysis of Al Qaeda's ideology and the practical utility of molecular biology. Al Qaeda is shown to advance a logic that is based not on the main schools of Islamic theology but rather on the result of applying Islamic principles to sociopolitical change, thereby re-interpreting the guidelines of Islamic law. Al Qaeda's philosophical underpinnings render non-combatants legitimate targets and inspire its followers to commit violent acts of destruction while being convinced they are fulfilling the ordained will of Allah. In conjunction with this ideological perspective, a discussion of modern biomedical research considers the technical challenges of applying scientific advances to the development and deployment of biological weapons consistent with Al Qaeda's operational history. This multidisciplinary analysis reveals that the reality of Al Qaeda challenges both the ideological and the technical constraints that have hitherto precluded a successful bioterrorism attack.

Cellular responses to EGFR inhibitors and their relevance to cancer therapy

EGFR is a trans-membrane receptor tyrosine kinase that belongs to the HER family of receptors. The EGFR family plays an essential role in normal organ development by mediating morphogenesis and differentiation. Unlike normal cells that have tight regulatory mechanisms controlling EGFR pathways, tumor cells often have dysregulated EGFR signaling through receptor overexpression and/or mutation. This leads to proliferation under adverse conditions, invasion of surrounding tissues, and increased angiogenesis as well as resistance to radiation and chemotherapy. Therefore, EGFR is a legitimate therapeutic target. Numerous EGFR inhibitors are under development, but to date only four of them are FDA-approved, including two that inhibit the receptor’s intracellular tyrosine kinase activity (gefitinib and erlotinib) and two that block extracellular ligand binding (cetuximab, and most recently panitumumab). In this review, we focus on how these different inhibitors affect EGFR signaling and the mechanisms by which they potentiate the effects of chemotherapy and radiation therapy. Numerous clinical trials have been conducted with these agents either as monotherapy, in combination with chemotherapy, or concurrently with radiation. Unfortunately, many of the clinical trials reported so far have shown at best limited gains; therefore, understanding the actions of these agents is essential to improving their efficacy in the treatment of cancers.

Illegal attack or legitimate target? Israel attacks Al Manar

“The bombing of Al Manar is a clear demonstration that Israel has a policy of using violence to silence media it doesn’t agree with. This action means media can become routine targets in every conflict. It is a strategy that spells catastrophe for press freedom and should never be endorsed by a government that calls itself democratic.” - Aidan White, General Secretary, International Federation of Journalists Among the many targets hit by Israel during the Israel-Hizbullah conflict were the headquarters of Al Manar, Hizbullah’s satellite television station (for the full story see Paul Cochrane). Also destroyed were relay stations in northern Lebanon used to broadcast two other Lebanese television stations, LBC and Al Mustaqbal. An Israeli military official later explained the second attack—which killed one LBC employee—reasoning that LBC may have been sharing relay facilities with Al Manar. These attacks were not surprising to most commentators on the war. While the bombing of the LBC and Al Mustaqbal facilities on Mount Terboul may have shocked some, few if any expected Al Manar, located in the heart of Beirut’s southern suburbs, to emerge from the conflict unscathed. Indeed, as some predicted, Al Manar’s central headquarters in southern Beirut were one of the first targets hit by Israel. The central question raised by these attacks on media outlets is when, if ever, is it appropriate and/or legal to deliberately target the media as part of a military campaign? Did Al Manar constitute a legitimate military target? Or did Israel cross the line in targeting a media outlet? What, exactly, constitutes a “legitimate” military target? And are critics of Israel’s strike against Al Manar correct when they allege that Israel’s actions against Al Manar create such a precedent that it endangers all media?

Improving the Performance of Indicator Groups for the Identification of Important Areas for Species Conservation

Indicator groups may be important tools with which to guide the selection of networks of areas for conservation. Nevertheless, the literature provides little guidance as to what makes some groups of species more suitable than others to guide area selection. Using distributional data on all sub-Saharan birds and mammals, we assessed factors that influence the effectiveness of indicator groups. We assessed the influence of threatened, endemic, range-restricted, widespread, and large-bodied species by systematically varying their number in indicator groups. We also assessed the influence of taxonomic diversity by systematically varying the number of distinct genera and families within the indicator groups. We selected area networks based on the indicator groups and tested their ability to represent a set of species, which, in terms of species composition, is independent of the indicator group. Increasing the proportion of threatened, endemic, and range-restricted species in the indicator groups improved effectiveness of the selected area networks; in particular it improved the effectiveness in representing other threatened and range-restricted species. In contrast increasing the proportion of widespread and large-bodied species decreased effectiveness. Changes in the number of genera and families only marginally affected the performance of indicator groups. Our results reveal that a focus on species of special conservation concern, which are legitimate conservation targets in their own right, also improves the effectiveness of indicator groups, in particular in representing other species of conservation concern.

DEMOCRATIC AUTHORIZATION AND CIVILIAN IMMUNITY1

In a recent analysis of the principle of civilian immunity, Igor Primoratz asks whether the circle of legitimate targets in war might be expanded so as to include at least some civilian bystanders. However Primoratz’ formulation of the ‘responsible bystander’ argument depends for its cogency on there being natural or non-acquired positive duties, and this is controversial. Furthermore, we feel that the citizens of a government unjustly at war are primarily and specially obliged to undermine that war, and that this is not simply a function of their being in the best position to do so, (which may not always be the case). Primoratz’ version of ‘responsible bystander’ cannot account for this. Here I develop an alternative formulation that does, and which is not reliant on controversial premises. I argue that to empower a government democratically is to assume a positive obligation to prevent that government from using its power to prosecute an unjust war, and that the neglect of this duty may render a significant portion of the duty-bound collective legitimate targets of necessary and proportionate violence. In closing I dispute Primoratz’ claim that this conclusion has “very little purchase on reality” or is irrelevant for practical purposes.

Requirement of KISS1 Secretion for Multiple Organ Metastasis Suppression and Maintenance of Tumor Dormancy

The KISS1 protein suppresses metastasis of several tumor models without blocking orthotopic tumor growth, but the mechanism remains elusive. For its role in human sexual maturation, KISS1 protein is secreted and processed to kisspeptins, which bind to the G protein-coupled receptor GPR54. We tested the hypothesis that KISS1 secretion is required for metastasis suppression via GPR54. KISS1 containing an internal FLAG epitope with (KFM) or without (KFMdeltaSS) a signal sequence was transfected into C8161.9 human melanoma cells, which do not express endogenous KISS1. Whole-cell lysates and conditioned medium from C8161.9(KFM) and C8161.9(KFMdeltaSS) cells were collected and analyzed for kisspeptins by immunoprecipitation and enzyme-linked immunosorbent assay. GPR54 levels were measured using real-time reverse transcription-polymerase chain reaction. The ability of conditioned medium from C8161.9(KFM) and C8161.9(KFMdeltaSS) cells to stimulate calcium mobilization in GPR54-expressing Chinese hamster ovary cells (CHO-G) and in C8161.9 cells was evaluated. Metastasis was monitored in athymic mice (groups of 10 per experiment) that were injected with C8161.9(KFM) or C8161.9(KFMdeltaSS) cells labeled with enhanced green fluorescent protein. Survival of mice injected with C8161.9 or C8161.9(KFM) cells was analyzed by Kaplan-Meier methods. Full-length KFM and KFMdeltaSS were detected in whole-cell lysates of C8161.9(KFM) and C8161.9(KFMdeltaSS) cells, respectively, but kisspeptins were detected only in conditioned medium of C8161.9(KFM) cells. In vivo, C8161.9(KFM), but not C8161.9(KFMdeltaSS), cells were suppressed for metastasis to lung, eye, kidney, and bone, with corresponding differences in mouse survival (median > 120 versus 42 days). C8161.9(KFM) cells seeded mouse lungs but did not form macroscopic metastases. Conditioned medium from C8161.9(KFM), but not C8161.9(KFMdeltaSS), cells stimulated calcium mobilization in CHO-G cells. GPR54 expression was low in C8161.9 cells, which were not stimulated by conditioned medium from C8161.9(KFM) cells. KISS1 secretion was required for multiple organ metastasis suppression and for maintenance of disseminated cells in a dormant state. The absence of GPR54 expression in C8161.9 cells (whose metastatic spread was suppressed by KFM) suggests that metastasis suppression is not mediated through this receptor. The results imply the existence of another KISS1 receptor and/or paracrine signaling. The findings raise the possibility that soluble KISS1, kisspeptins, or mimetics could be used to maintain tumor dormancy, rendering treatment of already disseminated tumor cells (i.e., micrometastases) a legitimate target.