Editorial
Remaining hurdles to effective cancer therapy Joanna Schaffhausen (Editor) Cancer is one of the leading causes of mortality worldwide, with more than 8 million deaths annually, per the World Health Organization. However, treatment of many types of cancer has improved dramatically over the past two decades and, since the mid-1990s, the cancer death rate has been decreasing steadily. Today, nearly half of all patients with cancer can expect to live for 5 or more years after their initial diagnosis. Still, many challenges remain in the pursuit of a cancer cure. Scientists have not been able to pinpoint a ‘cause’ for cancer, because it becomes clearer that cancer is a heterogeneous disease, involving many different types of cell, even within a single tumor. It can evolve with time and treatment, often necessitating combination therapies to battle the enemy on simultaneous different fronts. The treatments themselves have become more targeted, but serious, health-threatening adverse effects limit effective therapies and take a toll on patients. In this issue of Trends in Pharmacological Sciences (TiPS), we feature a variety of articles that examine some of the current hurdles in cancer therapy. One key issue concerns metastasis, or the spread of cancer beyond the initial tumor site. Treatment of cancer at the primary site is often effective, but metastatic cancer has proved difficult to combat and is typically fatal. It is becoming increasingly clear that the beginnings of metastasis are present in many cases of early disease, suggesting that there is potential to stop it in the initial stages. Yutong Sun and Li Ma review emerging understanding on the molecular machinery and therapeutic targets of metastasis. Regardless of tumor type, there are hallmark changes and similar processes involved as tumor cells escape from their initial site, travel to a new area, and establish residence with a supportive vascular system and microenvironment. In a separate article, Yihong Wan and Jing Y. Krzeszinski take a look at the specific processes involved in bone metastasis, which is one of the most frequent sites of metastatic disease. Bone metastases trigger severe pain and are also the major
reasons for pathologic fracture, life-threatening hypercalcemia, spinal cord compression, immobility, and ultimate mortality in patients. However, new therapies and emerging potential targets are offering new hope for improved treatment. As mentioned in the articles on metastasis, eradication of cancer stem cells (a distinct subpopulation of tumor cells that retain the ability to reproduce themselves and, thus, initiate new tumors) is an important but elusive goal of effective cancer treatment. Many cancer stem cells are enriched by conventional cancer therapy. In their review, Gong Peng and Yang Liu discuss how cancer stem cells and activated immune effector cells exhibit high activity of hypoxia-inducible factors (HIFs) in normoxic environments. HIF activity is critical in maintenance of cancer stem cells as well as differentiation and function of inflammatory cells, and, thus, targeting HIF is a promising avenue for cancer stem cell elimination. Finally, this issue of TiPS includes two different perspectives on a dangerous long-term complication from cancer chemotherapy: cardiotoxicity that can lead to heart failure. Anthracyclines and trastuzumab are two types of effective chemotherapy that sometimes also cause cardiotoxicity, although the mechanisms may be distinct. Luc Rochette and colleagues examine pathways involved in cardiotoxicity that include both ‘on-target’ and ‘off-target’ effects. They discuss how basic research into cardiotoxicity has revealed both underlying mechanisms that trigger cardiotoxicity and novel targets for anticancer therapy. In a related perspective article, Michael Ewer and Steven Ewer provide the clinician’s view on cardiotoxicity from chemotherapy and discuss how treating physicians adapt to the changing picture to provide the maximum benefit to their patients. TiPS would like to thank all the authors involved in this special focus on cancer therapy. We hope you, our readers, enjoy reading the articles as much as we have enjoyed putting them together.
Corresponding author: Schaffhausen, J. ([email protected]). 0165-6147/ ß 2015 Published by Elsevier Ltd. http://dx.doi.org/10.1016/j.tips.2015.04.008
Trends in Pharmacological Sciences, June 2015, Vol. 36 No. 6
v
Remaining hurdles to effective cancer therapy Joanna Schaffhausen (Editor) Cancer is one of the leading causes of mortality worldwide, with more than 8 million deaths annually, per the World Health Organization. However, treatment of many types of cancer has improved dramatically over the past two decades and, since the mid-1990s, the cancer death rate has been decreasing steadily. Today, nearly half of all patients with cancer can expect to live for 5 or more years after their initial diagnosis. Still, many challenges remain in the pursuit of a cancer cure. Scientists have not been able to pinpoint a ‘cause’ for cancer, because it becomes clearer that cancer is a heterogeneous disease, involving many different types of cell, even within a single tumor. It can evolve with time and treatment, often necessitating combination therapies to battle the enemy on simultaneous different fronts. The treatments themselves have become more targeted, but serious, health-threatening adverse effects limit effective therapies and take a toll on patients. In this issue of Trends in Pharmacological Sciences (TiPS), we feature a variety of articles that examine some of the current hurdles in cancer therapy. One key issue concerns metastasis, or the spread of cancer beyond the initial tumor site. Treatment of cancer at the primary site is often effective, but metastatic cancer has proved difficult to combat and is typically fatal. It is becoming increasingly clear that the beginnings of metastasis are present in many cases of early disease, suggesting that there is potential to stop it in the initial stages. Yutong Sun and Li Ma review emerging understanding on the molecular machinery and therapeutic targets of metastasis. Regardless of tumor type, there are hallmark changes and similar processes involved as tumor cells escape from their initial site, travel to a new area, and establish residence with a supportive vascular system and microenvironment. In a separate article, Yihong Wan and Jing Y. Krzeszinski take a look at the specific processes involved in bone metastasis, which is one of the most frequent sites of metastatic disease. Bone metastases trigger severe pain and are also the major
reasons for pathologic fracture, life-threatening hypercalcemia, spinal cord compression, immobility, and ultimate mortality in patients. However, new therapies and emerging potential targets are offering new hope for improved treatment. As mentioned in the articles on metastasis, eradication of cancer stem cells (a distinct subpopulation of tumor cells that retain the ability to reproduce themselves and, thus, initiate new tumors) is an important but elusive goal of effective cancer treatment. Many cancer stem cells are enriched by conventional cancer therapy. In their review, Gong Peng and Yang Liu discuss how cancer stem cells and activated immune effector cells exhibit high activity of hypoxia-inducible factors (HIFs) in normoxic environments. HIF activity is critical in maintenance of cancer stem cells as well as differentiation and function of inflammatory cells, and, thus, targeting HIF is a promising avenue for cancer stem cell elimination. Finally, this issue of TiPS includes two different perspectives on a dangerous long-term complication from cancer chemotherapy: cardiotoxicity that can lead to heart failure. Anthracyclines and trastuzumab are two types of effective chemotherapy that sometimes also cause cardiotoxicity, although the mechanisms may be distinct. Luc Rochette and colleagues examine pathways involved in cardiotoxicity that include both ‘on-target’ and ‘off-target’ effects. They discuss how basic research into cardiotoxicity has revealed both underlying mechanisms that trigger cardiotoxicity and novel targets for anticancer therapy. In a related perspective article, Michael Ewer and Steven Ewer provide the clinician’s view on cardiotoxicity from chemotherapy and discuss how treating physicians adapt to the changing picture to provide the maximum benefit to their patients. TiPS would like to thank all the authors involved in this special focus on cancer therapy. We hope you, our readers, enjoy reading the articles as much as we have enjoyed putting them together.
Corresponding author: Schaffhausen, J. ([email protected]). 0165-6147/ ß 2015 Published by Elsevier Ltd. http://dx.doi.org/10.1016/j.tips.2015.04.008
Trends in Pharmacological Sciences, June 2015, Vol. 36 No. 6
v
