Metastatic Latency, a Veiled Threat

Abstract

Metastatic relapse is observed in cancer patients with no clinical evidence of disease for months to decades after initial diagnosis and treatment. Disseminated cancer cells that are capable of entering reversible cell cycle arrest are believed to be responsible for these late metastatic relapses. Dynamic interactions between the latent disseminated tumor cells and their surrounding microenvironment aid cancer cell survival and facilitate escape from immune surveillance. Here, we highlight findings from preclinical models that provide a conceptual framework to define and target the latent metastatic phase of tumor progression. The hope is by identifying patients harboring latent metastatic cells and providing therapeutic options to eliminate metastatic seeds prior to their emergence will result in long lasting cures.

Technical Advancements for Studying Immune Regulation of Disseminated Dormant Cancer Cells

“…Although most tumors cover the same steps of metastatic dissemination (i.e., extravasation, dissemination through blood or lymphatics, intravazation, and establishment in the metastatic niche), the time required to form overt lesions significantly differs according to the tissue of origin and cancer subtypes. While breast, prostate, renal cell cancers, as well as sarcomas and melanomas show long latency and the time required to develop metachronous metastasis might reach 15 years, 85% of relapses from colon cancer are detected within 3 years (medium latency), and lung cancers often spread at distant sites within a few weeks (short latency) ( 1 , 3 – 5 ). When the time required for a DCC to form an overt metastasis after the removal of the primary tumor is long (arbitrarily usually set as 5 years), latency is often referred to as “dormancy”.…”

“…Moreover, a further boost in immunotherapy might come from a better understanding of the immune diversity in the TME and the way immune cells locally interact, as this can help to predict therapeutic responsiveness ( 91 , 100 ). Since immune cells are important in limiting metastatic outgrowth and keeping DCCs in an indolent state ( 5 , 26 , 101 , 102 ), it is tempting to foresee a role of immunotherapy in targeting dormant DCCs ( 103 ). However, this possibility is currently restrained by a limited understanding of how immune cells interact with DCCs.…”

Metabolic diversity within breast cancer brain-tropic cells determines metastatic fitness

“…The majority of disseminated tumor cells (DTCs) in the brain parenchyma perish. The surviving few may initiate synchronous metastases that are detected along with the primary tumor or adapt and stay latent for months to years before triggering a metachronous metastatic outbreak (Kienast et al, 2010;Kim et al, 2019;Massague ´and Obenauf, 2016). The survival dependencies of cancer cells with a similar genomic profile that have differentially adapted to the brain parenchyma are unknown.…”

Metastasis Relapse in Synovial Sarcoma of Parotid Gland Followed by Neuropathies and Tissue Damage: A Case Report

“…Through these events PNTS is promoted along with severe neuropathies. Metastatic relapse is observed in cancer patients with no clinical evidence of disease for months to decades after initial diagnosis and treatment [9]. Neuropathies and altered tumor microenvironment caused by radiotherapy and cancer cells plays an important role in latent distant metastasis and metastatic relapse in synovial sarcoma of parotid gland.…”