Tarin Lab: Clinical and Research Activities

Research interests and activities

In particular, Dr Tarin’s research has focused on fate-determining interactions between different cell lineages during embryonic development, wound healing and tumor formation. His early work described distinct sequential changes at the tumor-host interface accompanying cancer development in several organs (Refs 1&5). On the basis of these and other studies, described in his publications of the 1960’s and 1970’s (see below), he was the first to describe the concept of a dynamically interactive tumor microenvironment. His further work published in the 1980’s, 1990’s and since 2000 (detailed below), contributed to the widespread recognition of the pivotal significance of these microenvironmental interactions in the development, progression, and metastasis of cancers. He is also the first and only investigator to have ethically studied the fate of disseminating tumor cells and the distribution of metastases in living human subjects (Tarin D et al 1984,Cancer Res 44, 3584-3592). Subsequently he demonstrated that solitary dormant cancer cells residing in metastasis-free organs of tumor-bearing hosts retain tumorigenic and metastatic capability if retrieved and transplanted to suitable organs (Suzuki et al 2006, Ref#161). These experiments revealed that cancer cells are not omnipotent or fully autonomous and can only survive and grow, if they succeed in recruiting the sustained support of neighboring, non-neoplastic host cells. Tarin’s contributions to the cancer field carry the significant therapeutic implication that interventions which block signals mediating recruitment of host stromal cells into the tumor should amplify the growth-arresting effects of cancer cytotoxic agents, and enhance relapse-free survival rates Hence the body of work has had a unified theme and continues to have an upward momentum to the present time, using the latest techniques, as soon as they became available (e.g., in chronological order: immunocompromized mice, Southern and Western blotting, PCR, fluorescent genetic labeling of cells with GFP and RFP, high throughput gene expression analysis with oligonucleotide microarrays and gene silencing with small intereference RNA and ribozymes). Throughout his career, his work has sustained a sharp focus on obtaining information that could be useful diagnostically or therapeutically in human oncological medicine. His most recent work is on the molecular dialog between tumor cells and the host during primary and secondary tumor formation (See below Montel et al 2004, 2005, 2006, Refs 155, 157& 160); Suzuki et al 2006, 2007, Refs. 161, 163 & 164). This work substantiates predictions made over 40 years ago by Dr Tarin about the importance of the essential contribution of the neighboring host tissues to tumor development. Its objective is to define molecular targets for drugs that could arrest interactions mediating recruitment of host support for tumor growth. In addition, he has recently completed and published a study of inappropriate gene expression in a series of human breast cancers (Ref #170), a potential cause of mis-diagnosis and has submitted a paper on a new paradigm of immunocytotoxic treatment of cancer acting via the cancer stroma. ((Article #171). Simultaneously he has collaborated with colleagues in the UCSD Cancer Center on src oncogene addiction in pancreatic cancers and on suppression of TGF ? signaling in pancreatic cancer development.

Clinical academic work

Dr Tarin has also made contributions to the delivery of patient care both at UCSD and previously at Oxford University Hospitals in England. He initiated a multidisciplinary care group for breast cancer patients at Oxford consisting of pathologists, surgeons, medical oncologists, radiologists, radiotherapists, psychiatrists, nurses and other clinical care personnel, who systematically considered and decided every patient’s treatment at a weekly meeting. As Director of the Cancer Center at UCSD he built on this successful paradigm to create specialized cancer units comprised of experts on all major tumor types. These are now thriving and implement the clinical care vision based upon his research to achieve improvements in survival and reduction in morbidity at reasonable cost. He continues to participate in the discussions in the meetings of these specialized cancer units.