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academies
Journal of Medical Oncology & Therapeutics | Volume 4
Oncology & Cancer Therapy
International Conference on
March 18-19, 2019 | London, UK
Notes:
M
ultiple factors are involved in the development of
cancer. They may include carcinogens, host genetic risk,
chronic inflammation and others, which cause mutations
within cellular DNA. The mutant cancer cells flourish in the
cancer microenvironment (CM) consisting of fibroblasts,
lipocytes, immune cells, lymphatic and vascular vessels
and other parenchymal cells. Mutation gives rise to the
unique characteristics of cancer heterogeneity with various
clones competing to survive within the CM. By evading the
host immune surveillance and by its intrinsic proliferative
advantages using unique signaling pathways, cancer clones
grow by expansion. The cancer cells tend to spread first
through the sentinel lymph node (SLN) in over 90% of the
time, which serves as a primary gateway for the cancer cells
to proliferate and spread further to distant sites. Patients with
negative SLNs but subsequently develop distant metastasis
during follow-up indicate that their cancer cells have bypassed
the SLNs to spread through the vascular system. VEGF-C
has been found to induce lymph angiogenesis in the SLNs
and facilitate systemic metastasis. The interaction between
cancer cells and the immune system varies among different
patients and it undergoes continuous dynamic changes. The
relationship between the cytotoxic T cells (CTLs) and cancer
cells is highly complex and their molecular interactions have
been elucidated through the understanding of the CTLA-
4 and programmed death (PD-1) pathways. During cancer
progression and evolution in the host, the cancer cells have
maximized their ability to take advantage of the CTLA-4
and PD-1 pathways to proliferate while causing the CTLs to
undergo apoptosis and wither away so that the cancer cells
can grow without hindrance. Thus, aggressive cancer clones
have achieved the survival advantage as the ‘fittest’ clones
akin to Darwin’s survival of the fittest from the influence of
natural selection. The CM may exert the selective force to
favor the cancer clones to develop, similar to the principles of
directed evolution of enzymes and antibodies The molecular
relationshipbetweencancer growthandCMaswell as thehost
influence such as the immune system on cancer progression
may be studied by using multiplexed microscopy, genomic
profiling, microRNA analysis and gene exon sequencing. To
date, blockade of the immune checkpoint pathways such as
ipilimumab (anti-CTLA-4), pembrolizumab and nivolumab
(both anti-PD-1) have resulted in significant tumor responses
with subsequent FDA approval of these drugs. The immune
system and cancer growth are so complex that perhaps
artificial intelligence needs to be developed to elucidate the
proliferation of cancer cells in relationship to the structure
and physiology of the lymphatic system in a new field, which
may be coined as Oncolymphology.
Speaker Biography
Stanley P L Leong is board certified in surgery and is an internationally recognized
surgical oncologist with expertise in melanoma. He specializes in sentinel lymph
node surgery and immunotherapy for patients with advanced melanoma. He has
lectured nationally and internationally on new advances in the treatment of malignant
melanoma and the use of selective sentinel lymphadenectomy. As Associate Director
of CPMC’s Center for Melanoma Research and Treatment, he collaborates with other
investigators including Mohammed Kashani-Sabet on a new integrated research
program at CPMCRI aimed at developing novel combination therapies for aggressive
and metastatic tumors, including melanomas. He is the founding member and
president of the Sentinel Node Oncology Foundation. He has chaired and co-chaired
the biennial International Cancer Metastasis Congress since 2005 with emphasis in the
mechanisms of cancer metastasis through the lymphovascular system.
e:
leongsx@sutterhealth.orgStanley P L Leong
California Pacific Medical Center and Research Institute, USA
Cancer metastasis from the primary site to the sentinel lymph nodes and beyond in
relationship to the immune system