Review

Authors: Scott Valastyan, Robert A Weinberg

Metastases represent the end products of a multistep cell-biological process termed the invasion-metastasis cascade, which involves dissemination of cancer cells to anatomically distant organ sites and their subsequent adaptation to foreign tissue microenvironments. Each of these events is driven by the acquisition of genetic and/or epigenetic alterations within tumor cells and the co-option of nonneoplastic stromal cells, which together endow incipient metastatic cells with traits needed to generate macroscopic metastases. Recent advances provide provocative insights into these cell-biological and molecular changes, which have implications regarding the steps of the invasion-metastasis cascade that appear amenable to therapeutic targeting.

Topics: Animals; Basement Membrane; Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Prognosis; Signal Transduction; Stromal Cells

PubMed: 22000009
DOI: 10.1016/j.cell.2011.09.024

Review

Authors: Sean R Stowell, Tongzhong Ju, Richard D Cummings...

Neoplastic transformation results in a wide variety of cellular alterations that impact the growth, survival, and general behavior of affected tissue. Although genetic alterations underpin the development of neoplastic disease, epigenetic changes can exert an equally significant effect on neoplastic transformation. Among neoplasia-associated epigenetic alterations, changes in cellular glycosylation have recently received attention as a key component of neoplastic progression. Alterations in glycosylation appear to not only directly impact cell growth and survival but also facilitate tumor-induced immunomodulation and eventual metastasis. Many of these changes may support neoplastic progression, and unique alterations in tumor-associated glycosylation may also serve as a distinct feature of cancer cells and therefore provide novel diagnostic and even therapeutic targets.

Topics: Animals; Cell Transformation, Neoplastic; Epigenesis, Genetic; Glycosylation; Humans; Neoplasm Proteins; Neoplasms

PubMed: 25621663
DOI: 10.1146/annurev-pathol-012414-040438

Review

Authors: Andriy Marusyk, Michalina Janiszewska, Kornelia Polyak...

Advances in our understanding of molecular mechanisms of tumorigenesis have translated into knowledge-based therapies directed against specific oncogenic signaling targets. These therapies often induce dramatic responses in susceptible tumors. Unfortunately, most advanced cancers, including those with robust initial responses, eventually acquire resistance to targeted therapies and relapse. Even though immune-based therapies are more likely to achieve complete cures, acquired resistance remains an obstacle to their success as well. Acquired resistance is the direct consequence of pre-existing intratumor heterogeneity and ongoing diversification during therapy, which enables some tumor cells to survive treatment and facilitates the development of new therapy-resistant phenotypes. In this review, we discuss the sources of intratumor heterogeneity and approaches to capture and account for it during clinical decision making. Finally, we outline potential strategies to improve therapeutic outcomes by directly targeting intratumor heterogeneity.

Topics: Drug Resistance, Neoplasm; Genetic Heterogeneity; Humans; Mutation; Neoplasm Proteins; Neoplasm Recurrence, Local; Neoplasms; Phenotype

PubMed: 32289271
DOI: 10.1016/j.ccell.2020.03.007

Authors: Robert Kruger

Topics: Databases, Genetic; Genes, Neoplasm; Genome, Human; Humans; Neoplasms

PubMed: 29625043
DOI: 10.1016/j.cell.2018.03.048

Authors: Joan Massagué, Eduard Batlle, Roger R Gomis...

Topics: Animals; Epithelial-Mesenchymal Transition; Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Neoplastic Cells, Circulating

PubMed: 28085221
DOI: 10.1002/1878-0261.12024

Review

Authors: Janice N Cormier, Raphael E Pollock

Sarcomas are a heterogeneous group of rare tumors that arise predominantly from the embryonic mesoderm. They present most commonly as an asymptomatic mass originating in an extremity but can occur anywhere in the body, particularly the trunk, retroperitoneum, or the head and neck. Pretreatment radiologic imaging is critical for defining the local extent of a tumor, staging the disease, guiding biopsies, and aiding in diagnosis. Core-needle biopsy is the preferred biopsy technique for diagnosing soft tissue sarcomas. The American Joint Committee on Cancer (AJCC) staging system for soft tissue sarcomas is based on histologic grade, the tumor size and depth, and the presence of distant or nodal metastases. Despite improvements in local control rates with wide local resections and radiation therapy, metastasis and death remain a significant problem in 50% of patients who present with high-risk soft tissue sarcomas. The most common site of metastasis is the lungs, and metastasis generally occurs within two to three years after the completion of therapy. Progress in the molecular characteristics of these tumors should in the near future translate into molecularly based therapies that can be incorporated into standard treatment strategies.

Topics: Gastrointestinal Neoplasms; Humans; Incidence; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Retroperitoneal Neoplasms; Sarcoma

PubMed: 15061599
DOI: 10.3322/canjclin.54.2.94

Review

Authors: Carlo Patriarca, Giacomo Maria Pini, Giario Conti...

The idea that neoplasms grow, becoming unresectable through dissemination, which is initially loco-regional, and systemic only in a later stage, is historically at the basis of the radical surgery - where, by 'radical', the old surgery meant the complete removal of the tumor and, in practice, aggressive surgery. Halsted's "radical mastectomy", as well as many principles of surgical anatomy of the first decades of the twentieth century, obey to an idea of tumor progression as a linear process taking place in continuity and contiguity, where the various anatomical layers and the peritumoral desmoplastic reaction are mistaken for a wall of defense against the neoplasm's dissemination, capable of containing and orienting it. However, the investigations of the processes of invasion and metastasis by Rudolf Virchow and Stephel Paget helped to reorient surgical approaches.

Topics: Breast Neoplasms; Female; History, 20th Century; Humans; Mastectomy; Neoplasm Invasiveness; Neoplasm Metastasis

PubMed: 33393528
DOI: 10.32074/1591-951X-111

Review

Authors: Kimberly H Allison, George W Sledge

Cancer heterogeneity, long recognized as an important clinical determinant of patient outcomes, was poorly understood at a molecular level. Genomic studies have significantly improved our understanding of heterogeneity, and have pointed to ways in which heterogeneity might be understood and defeated for therapeutic effect. Recent studies have evaluated intratumoral heterogeneity within the primary tumor, as well as heterogeneity observed between primary and metastasis. The existence of clonal heterogeneity in the primary and metastasis also affects response to therapy, since the Darwinian pressures of systemic therapy result in clonal selection for initially rare variants. Novel technologies (such as measurements of circulating tumor cells and circulating tumor DNA) may allow physicians to monitor the emergence of clonal subtypes and intervene at an early point to improve patient prognosis.

Topics: Biomarkers, Tumor; DNA, Neoplasm; Genetic Heterogeneity; Genetic Predisposition to Disease; Humans; Neoplasms

PubMed: 25224475
DOI: No ID Found

Review

Authors: Fang Huang, Gang Wu, Kunyu Yang...

The standard treatment choice for cancer metastasis has been systemic management, including cytotoxic chemotherapy, hormonal manipulation, and targeted therapy. Emerging evidence has shown an oligometastatic state, an intermediate state between limited primary cancer and polymetastatic cancer, in which local therapy for metastatic lesions results in satisfactory survival comparable to non-metastatic disease. We provide a comprehensive introduction of evidence from experimental and clinical studies in favor of the oligometastatic phenotype, we review the efficacy and safety of surgery and stereotactic body radiotherapy in the treatment of oligometastases, and finally, we discuss the way to differentiate the oligometastatic state from polymetastasis.

Topics: Humans; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasms; Prognosis

PubMed: 25359216
DOI: 10.1186/s13014-014-0230-6

Review

Authors: Samer Tohme, Richard L Simmons, Allan Tsung...

Surgery is a crucial intervention and provides a chance of cure for patients with cancer. The perioperative period is characterized by an increased risk for accelerated growth of micrometastatic disease and increased formation of new metastatic foci. The true impact for cancer patients remains unclear. This review summarizes the often fragmentary clinical and experimental evidence supporting the role of surgery and inflammation as potential triggers for disease recurrence. Surgery induces increased shedding of cancer cells into the circulation, suppresses antitumor immunity allowing circulating cells to survive, upregulates adhesion molecules in target organs, recruits immune cells capable of entrapping tumor cells, and induces changes in the target tissue and in the cancer cells themselves to enhance migration and invasion to establish at the target site. Surgical trauma induces local and systemic inflammatory responses that can also contribute to the accelerated growth of residual and micrometastatic disease. Furthermore, we address the role of perioperative factors, including anesthesia, transfusions, hypothermia, and postoperative complications, as probable deleterious factors contributing to early recurrence. Through the admittedly limited understanding of these processes, we will attempt to provide suggestions for potential new therapeutic approaches to target the protumorigenic perioperative window and ultimately improve long-term oncological outcomes. .

Topics: Cell Movement; Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Micrometastasis; Neoplasm Recurrence, Local; Neoplasm, Residual; Neoplasms; Neoplastic Cells, Circulating

PubMed: 28330928
DOI: 10.1158/0008-5472.CAN-16-1536