Amit Lab in Action
Our research focus is split evenly between experimental cancer cell biology and studying tumor microenvironment subpopulations using computational biology approaches. We develop new experimental methods to isolate and sequence neural niche subpopulations and apply analytical approaches to study how solid tumors sculpt their microenvironment. We focus mainly on head and neck cancer to understand the role of the peripheral nervous system in the evolution of invasion, metastasis, and response to chemotherapy. Our goal is to understand the role of neural signaling in tumor evolution so that we can exploit these signals for therapeutic vulnerabilities and enhance cancer therapy. We fully expect that applying these tools to patients will ultimately inform key areas of cancer research including the prevention and treatment of cancer.
Experimental Models used for Neural-Cancer Cell Interaction
One main reason that understanding mechanisms of neural tracking is
challenging is the lack of reliable and reproducible experimental
models for neural invasion. The in vitro dorsal root ganglia (DRG)
assay (figure), designed for studying the neurotropic ability of
cancer cells, also enables modulation of paracrine signaling by
controlling chemoattractants and by signaling between cancer cells and
the DRG. Neurite outgrowth, directionality, and Euclidean velocity of
cancer cells can be measured before cancer¨Cneuron contact has been
established. However, the importance of various cellular components in
the classical perineural niche, including Schwann cells and
fibroblasts, cannot be directly addressed in this model.
Cancer cell invasion along the neurons of the dorsal root ganglia (DRG)
In Vitro Modeling of Cancerous Neural Invasion: The Dorsal
Root Ganglion Model
Solid tumors disseminate in three main ways: direct invasion, lymphatic spread, and hematogenic spread. However, there is a fourth means of cancer spread that is frequently disregarded: dissemination along nerves. This??shows the use of the dorsal root ganglia (DRG)/cancer cell model in pancreatic ductal adenocarcinoma.
Evolution of Malignant Precursor Lesion that Promotes Cancer Cell Invasion into the Nerve
As a malignant precursor lesion evolves, the perineural niche starts
to assemble to form a cellular and biochemical microenvironment that
can eventually promote cancer cell invasion into the nerve (panel a).
At a certain point, these neurogenic cues initiate axonogenesis, which
is accompanied by the recruitment of stromal cells typical of the
perineural niche (panel b). Subsequent malignant transformation
results in the release of multiple chemotactic cues, which promotes
further recruitment of inflammatory cells to establish the perineural
niche (panel c). Within the niche, an injured nerve serves as a portal
for invasion while neural homeostasis including Wallerian degeneration
and nerve regeneration is maintained (panel d). At the perineural
niche, the injured nerve maintains regeneration via nerve growth
factor secretion that further nourishes the inflammatory response and
leads to immune cell recruitment.
Current Studies
Phase II Randomized, Placebo- Controlled Study of Intralesional Nivolumab for High-risk Oral Premalignant Lesions
The goal of the trial is to evaluate the antitumor efficacy of intralesional injections of nivolumab in patients with high-risk oral premalignant lesions.
Contact: Mary Reyes Necesito
Psilocybin-Assisted Psychotherapy in Patients With Advanced Cancer on Maintenance Therapy
The goal of the trial is to learn about the feasibility, safety, and effects of psilocybin-assisted psychotherapy on depression and/or anxiety in participants who are being treated for advanced cancer.
Randomized Phase III Trial of Neoadjuvant Immunotherapy With Response-Adapted Treatment Versus Standard-of-Care Treatment for Resectable Stage III/IV Cutaneous Squamous Cell Carcinoma
The goal of the trial is to determine if neoadjuvant immunotherapy combined with response-adapted oncologic surgery improves site-reported event-free survival compared to standard-of-care surgery in resectable stage III/IV cutaneous squamous cell carcinoma (CSCC).
TRIPS - Treatment to Improve Depression and/?or Anxiety Using Psilocybin-assisted Psychotherapy in Cancer Survivors
This clinical research study is to learn about the feasibility, safety, and effects of psilocybin-assisted psychotherapy for cancer survivors with depression and/or anxiety.
Contact: Veronica Vallone
Psilocybin-Assisted Psychotherapy for Improving Depression and/or Anxiety in Patients Receiving Maintenance Therapy for Advanced Cancers, TRIP Trial
This Phase II trial tests the safety and side effects of psilocybin in combination with psychotherapy compared to placebo (niacin [a B vitamin]) in combination with psychotherapy for improving depression and/or anxiety in patients who are on maintenance therapy for cancers that may have spread from where it first started to nearby tissue, lymph nodes or distant parts of the body (advanced). Psilocybin is a substance being studied for the treatment of anxiety or depression in patients with cancer. It is taken from the mushroom Psilocybe mexicana.