Around 80% of viral cancers occur in countries with emerging economies such as LMICs. An important subset of virally induced malignancies occurs in the context of HIV/ AIDS (AIDS associated Malignancies/ AM). Latin America have a high prevalence of AIDS-associated Malignancies caused by viruses (including HR-HPV, EBV, KSHV) which tend to disproportionally affect underprivileged and socially vulnerable populations. The current consortium addresses the need of developing research strength in AIDS associated Malignancies while developing a critical mass of independent basic, translational and clinical AIDS-malignancies researchers of Argentina. The current U54 will focus in the career development of junior scientists belonging to an existing consortium of UM CFAR with Argentina Labs through the development of mentored research focusing in the general theme and cancer type of ?Basic, translational and Clinical research and training network in virally- induced AIDS-defining malignancies disproportionally affecting Argentina populations with highest risk of HIV/ AIDS?. In the case of Buenos Aires this is both the MSM population with a 11% HIV-infection incidence and the transgender women (TGW) population with an HIV-infection incidence of 37% which are at also the highest risk for infection with oncoviruses KSHV and HR-HPV, and to develop KS and anogenital carcinoma. It will further develop areas emerging from highly complementary and integrated current research of the consortium projects supported by highly tailored Career Enhancement and Shared Resources Cores that will leverage the outstanding research, human resources and infrastructure for HIV/AIDS and viral oncology research available at UM's CFAR, Sylvester Cancer Center, Argentina institutions and the powerful network of Argentine US scientists in USA associated with the consortium. Its components will include an Administrative core, a career enhancement core, a shared resource core and three projects of mentored research that will leverage and enhance the scientific and clinical capacity of the network, generating and leveraging a repository of clinical samples and longitudinal cohort that will enable to correlate clinical findings with molecular/genetic data.
Aim 1 : To develop research capacity in AM by developing the career of a critical mass of junior researchers in the context of shared resources and scientific networks provided by the consortium institutions.
Aim 2 : research on ?Viral induced AIDS-defining malignancies disproportionally affecting populations in Argentina with the highest risk of HIV/ AIDS? to elucidate molecular and cellular mechanisms of oncogenesis, identify therapeutic targets, prevent cancer, facilitate diagnosis and treatment. P1: Oncogenic signaling networks in AIDS-associated viral cancers as targets of chemoprevention and treatment. P2: Molecular, viral and genetic epidemiology of virally induced AIDS-defining cancers affecting Argentina population with highest risk for HIV infection. P3: Defining the role of lectin-glycan interactions in virally induced AIDS-associated cancers.
The research on the present consortium represents a combination of unique collaborative efforts by groups of scientists and institutions to advance the knowledge of certain cancers that are induced by viruses and can affect those individuals who are at the highest risk of HIV infection and of AIDS, generally associated with risky sexual practices. These two cancers are the Kaposi's sarcoma caused by a herpesvirus and anogenital carcinoma caused by a papillomavirus. The research will help to understand the mechanisms that these viruses unravel to cause cancer, undertand the mechanisms of its transmission and therefore open new avenues for treatment and prevention