Any type of advanced lung cancer is bad news, but a diagnosis of small cell lung cancer (SCLC) is a particularly grim one to receive. About 30 years have passed since any new treatments for SCLC were developed, and patients’ responses to standard chemotherapy with etoposide and cisplatin are short-lived. Hopefully, this will change soon.
If you have not yet heard of cancer stem cells (CSCs), often considered to be the real culprits in cancer, it is about time you do. CSCs are stem cells found in tumors. Drugs that target them are showing promise in clinical trials. More on that later; first, let’s introduce the concept of stem cells:
All normal tissues in our bodies develop from a small number of very special cells known as stem cells. Stem cells can divide a seemingly unlimited number of times. Continue reading…
A promising stem cell-based immunotherapy against melanomas has been fast-tracked by the U.S. Food and Drug Administration (FDA), based on previous clinical trials showing that it may double 5-year survival rates to about 50%. The upcoming phase III clinical trial will accept 250 people with melanomas that have spread; enrollment is expected to begin in early 2014. This experimental immunotherapy uses a mixture of a person’s own cells: cancer stem cells from his or her tumor, which are thought to be behind the spread of tumors, and immune system cells from the blood, which learn to recognize the cancer stem cells. These cancer stem cells are inactivated to keep them from forming new tumors, then the mixture is injected back into the patient. The reintroduced immune system cells then focus an attack on the cancer stem cells that remain in the tumor, which helps keep them from spreading.
A new clinical trial will investigate the safety of vantictumab (OMP-18R5), a new lung cancer drug targeting cancer stem cells (CSCs). CSCs, the actively multiplying cells responsible for generating tumors, are thought to be central in cancer relapse by ‘repopulating’ tumors, even if the bulk of the tumors cells are destroyed during treatment. Vantictumab blocks the Wnt pathway, a key molecular signaling pathway used by CSCs. Patients with previously treated advanced non-small cell lung cancer (NSCLC) will receive vantictumab in combination with the chemotherapy agent docetaxel (Taxotere). In addition to the safety of the drug combination, the trial will also investigate how effective it is and whether any biomarkers predict how well patients respond.
Mesothelioma is a form of lung cancer strongly associated with exposure to asbestos. Even though asbestos has been banned or heavily regulated in most developed nations, due to delayed onset, the number of mesothelioma cases is predicted to climb until around 2020. In the UK, which has the highest mesothelioma incidence worldwide, two new clinical trials are aiming to find treatments for the disease. The Meso2 trial will investigate ganetespib, while the COMMAND trial will examine defactinib. Defactinib specifically targets cancer stem cells, which often survive cancer treatment and cause cancer recurrence. The drug may therefore help prevent relapse after first-line therapy.
Gammaitoni L, Giraudo L, Leuci V, Todorovic M, et al. Clinical Cancer Research. Jun 21, 2013.
“Purpose: We investigate the unknown tumor-killing activity of Cytokine-Induced Killer (CIK) cells against autologous metastatic melanoma (mMel) and the elusive subset of putative cancer stem cells (mCSCs). Experimental Design: We developed a preclinical autologous model using same patient-generated CIK cells and tumor targets to consider the unique biology of each patient/tumor pairing. In primary tumor cell cultures we visualized and immunophenotipically defined a putative mCSC subset using a novel gene-transfer strategy that exploited their exclusive ability to activate the promoter of stemness gene Oct4.”
Zhao J, Ma MZ, Ren H, Liu Z, et al. Clin Cancer Res. Jun 17, 2013.
Approximately one third of the patients with advanced non–small cell lung carcinoma (NSCLC) will initially respond to platinum-based chemotherapy, but virtually all tumors will progress (acquired resistance). The remainder will progress during initial treatment (primary resistance). In this study, we test whether the treatment can be improved by inhibiting hepatoma-derived growth factor (HDGF). Our data support the hypothesis that cancer stem cells (CSC) are a mechanism for chemotherapy resistance and suggest HDGF may be a target for repressing CSCs to prevent relapse of NSCLC sensitive to chemotherapy.
Zhao J, Ma MZ, Ren H, Liu Z, et al. Clin Cancer Res. May 21, 2013.
“Approximately 1/3 of the patients with advanced non-small cell lung cancer (NSCLC) will initially respond to platinum-based chemotherapy, but virtually all tumors will progress (acquired resistance). The remainder will progress during initial treatment (primary resistance). In this study, we test whether the treatment can be improved by inhibiting hepatoma-derived growth factor (HDGF).”