Targeting Apoptotic Signaling Pathways in Human Lung Cancer

Abstract

Lung carcinoma is the leading cause of carcinoma death in the world. Despite recent advances in understanding the molecular biology of lung cancer and the introduction of new therapeutic agents for its treatment, its dismal 5-year survival rate has not changed substantially. Clinical approaches have not significantly improved the survival of patients with advanced lung cancer. However, recent discoveries about the molecular mechanisms responsible for lung cancer initiation and proliferation have unveiled new targets for therapy. One of the hallmark features of cancer cells is their ability to evade programmed cell death or apoptosis. Alterations in pro- and anti-apoptotic pathways are common in cancer cells and defects in regulation of apoptosis have been implicated in both lung tumorigenesis and drug resistance. Thus, targeting apoptosis through the direct or indirect manipulation of the pro-apoptotic machinery offers a novel strategy for treatment. This mini review summaries the molecular events that contribute to drug-induced apoptosis and how lung tumors evade apoptotic death followed by an analysis of the implications for treatment.

Targeting PKCε by miR‐143 regulates cell apoptosis in lung cancer

“…Imbalance of cell proliferation and apoptosis had been implicated in multiple cancers, including lung cancer, the most common one in human beings [1]. It is suggested that both genetic [2] and environmental [3] factors play critical roles in the etiology of lung cancer.…”

PNAS-4, an Early DNA Damage Response Gene, Induces S Phase Arrest and Apoptosis by Activating Checkpoint Kinases in Lung Cancer Cells

“…Despite recent advances in understanding the molecular biology of lung cancer and the introduction of new therapeutic agents for its treatment, its dismal 5-year survival rate has not changed substantially (1). Clinical approaches have not significantly improved the survival of lung cancer patients.…”

“…Clinical approaches have not significantly improved the survival of lung cancer patients. However, recent discoveries regarding the molecular mechanisms responsible for lung cancer initiation and proliferation have unveiled new targets for therapy (1). Emerging evidence suggests that alterations in pro-and anti-apoptotic pathways are common in cancer cells, and defects in regulation of apoptosis have been implicated in tumorigenesis and drug resistance (1)(2)(3).…”

Quercetin inhibits a large panel of kinases implicated in cancer cell biology

“…Many cancer types also display intrinsic resistance to proapoptotic stimuli even before metastasising, including NSCLC (43)(44)(45), melanoma (46,47), pancreatic cancer (48,49), oesophageal cancer (50) and glioma (51,52). Apart from the lack of response to apoptotic drugs, many cancers also develop an acquired chemoresistance during chronic treatments: the multidrug resistance (MDR) phenotype, which is a phenomenon caused by decreased intracellular drug accumulation in the cancer cells due to enhanced drug efflux (53,54).…”

“…Of these eight cancer cell lines, we previously demonstrated high levels of resistance to pro-apoptotic stimuli for the human U373 and T98G glioblastoma cells (50,62), the A549 NSCLC (15,44) and the SKMEL-28 melanoma (47). In the same manner, we demonstrated the sensitivity to proapoptotic stimuli of the human MCF-7 breast cancer (63), the PC-3 prostate cancer (63), and the mouse B16F10 melanoma (47) cell lines.…”