To accelerate our endeavors to overcome cancer, Chinese Journal of Cancer has launched a program of publishing 150 most important questions in cancer research and clinical oncology. In this article, nine more questions are presented as followed. Question 6. Why do nasopharyngeal carcinomas rarely metastasize to the brain? Question 7. Can distant spread of cancer cells be blocked by inhibiting the remodeling of high endothelial venules in the sentinel lymph node? Question 8. What sort of live-imaging techniques can be developed to directly observe the dynamic processes of metastasis? Question 9. How does chronic hepatitis prevent liver metastasis from colorectal cancer? Question 10. How many types of host cells contribute to forming the pre-metastatic niche in the lung favorable for metastasis? Question 11. Why do cancers rarely metastasize to the small bowel? Question 12. Why do glioblastomas rarely metastasize outside the central nervous system? Question 13. Despite increased understanding of the molecular genetic events leading to the development and progression of high-grade gliomas, these tumors are the most therapeutically refractory among all human cancers. What then would be the most effective therapeutic approaches to treat what in essence can be regarded as a whole brain malignancy, since even a surgical resection of greater than 99% of tumor tissues is invariably associated with recurrence? Question 14. The blood–brain barrier (BBB) effectively limits a wide variety of potential therapeutic agents from reaching glioma cells widely dispersed in the brain. What therapeutic approaches can be used to breach the BBB and allow therapeutic agents to seek out and kill these tumor cells?

Since the beginning of 2017, Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology, which sparkle diverse thoughts, interesting communications, and potential collaborations among researchers all over the world. In this article, 10 more questions are presented as followed. Question 57. What are the major stresses that drive the formation, progression, and metastasis of a cancer? Question 58. What is the mechanism responsible for altering an acidic intracellular pH and a basic extracellular pH in normal tissue cells to a basic intracellular pH and an acidic extracellular pH in cancer cells, a fundamental and yet largely ignored phenomenon? Question 59. Where are the tumor-associated plasma microRNAs from in cancer patients? Question 60. Can we identify mechanisms employed by tumor subpopulations to evade standard therapies and seed relapse/metastatic tumors before treatment? Question 61. Why are mutation rates in epidermal growth factor receptor (EGFR) and erb-b2 receptor tyrosine kinase 2 (ERBB2) higher in lung cancer from never smokers than that from smokers? Question 62. Does tumor vasculogenic mimicry contribute to the resistance against antiangiogenic therapy in renal cancer? Question 63. What molecular targeted drugs would be effective for non-clear cell renal cell carcinoma (RCC), especially metastatic papillary RCC and chromophobe RCC? Question 64. Can it be more effective by targeting both the vascular endothelial growth factor receptor (VEGFR) and MET signaling pathways in sporadic metastatic papillary renal cell carcinoma (RCC)? Question 65. What are the predictive biomarkers that may be used to identify the renal cell carcinoma (RCC) patients who can benefit from immune checkpoint inhibitor treatment? Question 66. How do we identify predictive molecular biomarkers to stratify clear cell renal cell carcinoma patients for targeted therapies?

Since the beginning of 2017, Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology, which sparkle diverse thoughts, interesting communications, and potential collaborations among researchers all over the world. In this article, 9 more questions are presented as followed. Question 67. How could we overcome the resistance of hepatocellular carcinoma against chemotherapeutics? Question 68. Is pursuit of non-covalent small-molecule binders of RAS proteins viable as a strategy of cancer drug discovery? Question 69. In what oligomeric structures do RAS proteins signal? Question 70. How can we achieve non-invasive early detection and diagnosis of lung cancer? Question 71. Does genetic information influence the volatolome enabling diagnosis of lung cancer with genetic mutations via cell headspace or breath analysis? Question 72. Is heavy ion beam radiotherapy effective to kill cancer stem cells? Question 73. Is there any diversity among different types of cancer in terms of sensitivity to heavy ion beam radiotherapy? Question 74. Can targeted alpha-particle therapy augment the effect of carbon ion radiotherapy on malignancies? Question 75. How does chromosomal instability drive tumor progression?

To accelerate our endeavors to overcome cancer, Chinese Journal of Cancer has launched a program of publishing 150 most important questions in cancer research and clinical oncology. In this article, 6 more questions are presented as followed. Question 25: Does imprinting of immune responses to infections early in life predict future risk of childhood and adult cancers? Question 26: How to induce homogeneous tumor antigen expression in a heterogeneous tumor mass to enhance the efficacy of cancer immunotherapy? Question 27: Could we enhance the therapeutic effects of immunotherapy by targeting multiple tumor antigens simultaneously or sequentially? Question 28: Can immuno-targeting to cytokines halt cancer metastasis? Question 29: How can we dynamically and less-invasively monitor the activity of CD8+ T killer cells at tumor sites and draining lymph nodes? Question 30: How can the immune system destroy the niches for cancer initiation?

Since the beginning of 2017, Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology, which sparkle diverse thoughts, interesting communications, and potential collaborations among researchers all over the world. In this article, 10 more questions are presented as followed. Question 40. Why do mice being used as tumorigenesis models raised in different places or different conditions possess different tumor formation rate? Question 41. How could we generate more effective anti-metastasis drugs? Question 42. What is the molecular mechanism underlying heterogeneity of cancer cachexia in patients with the same pathologic type? Question 43. Will patients with oligo-metastatic disease be curable by immunotherapy plus stereotactic body radiotherapy? Question 44. Can the Warburg effect regulation be targeted for cancer treatment? Question 45. Why do adenocarcinomas seldom occur in the small intestine? Question 46. Is Epstein–Barr virus infection a causal factor for nasal natural killer/T cell lymphoma formation? Question 47. Why will not all but very few human papillomavirus-infected patients eventually develop cervical cancer? Question 48. Why do cervical carcinomas induced by human papilloma virus have a low mutation rate in tumor suppressor genes? Question 49. Can viral infection trigger lung cancer relapse?