The 150 most important questions in cancer research and clinical oncology series: questions 6–14

To accelerate our endeavors to overcome cancer,Chinese Journal of Cancer has launched a program of publishing 150most 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?

The 150 most important questions in cancer research and clinical oncology series:questions 15-24

To accelerate our endeavors to overcome cancer,Chinese Journal of Cancer has launched a program of publishing 150most important questions in cancer research and clinical oncology.In this article,10 more questions are presented as follows.Question 15:Can tumor-induced erythrogenesis provide qualified red blood cells for carrying oxygen to distant organs?Question 16:Can we overcome tumor resistance to platinum-containing antineoplastic drugs by activating the sensitivity factors in the tumor?Question 17:How can a cancer cell stay dormant for years?Question 18:Why do cancer cells use distinct transcriptomic and proteomic programs to reach the same metastatic phenotype?Question 19:Why do some cancers regress spontaneously?Question 20:What are the regulatory mechanisms occurring in donor cells that determine selective sorting of biological content into vesicles and their biological consequences in recipient cells?Are the genetic transfer and exchange of biological messages between cells transient?Is the phenotypic manipulation of recipient cells temporary or prolonged and persistent?If extracellular vesicles possess immune-modulatory potential,how could they be exploited for immune interventions and cancer immunotherapy?Presumably the cargo of extracellular vesicles reflects the cells of their origin and can be used for cancer diagnosis,how could the uniform/stringent capture criteria be met universally for applying EVs in point-of-care diagnostics for cancer patients?Question 21:Can we use self-sampling technologies to monitor the tumor genetic alterations for more precise targeted therapy?Can we cure a heterogeneous tumor by sequentially targeting the driver molecules?Question 22:Can we postpone the onset of non-infection-related cancers?Question 23:How many types of cells can jointly form the tumor vasculature to provide blood supply for tumor progression?Question 24:How tumor cells transmit their epigenetic features to daughter cells and maintain the malignant phenotype?

The 150 most important questions in cancer research and clinical oncology series:questions 50-56

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, seven more questions are presented as followed. Question50. When tumor cells spread from primary site to distant sites, are they required to be "trained" or "armed" in the bone marrow niche prior to colonizing soft tissues? Question 51. Are there tipping points during cancer progression which can be identified for manipulation? Question 52. Can we replace molecular biomarkers by network biomarkers?Question 53. Are conventional inhibitors of key cellular processes such as cell proliferation and differentiation more effective than targeted chemotherapeutics that antagonize the downstream cell signaling network via cell-surface receptors such as epidermal growth factor receptor(EGFR), vascular endothelial growth factor receptor(VEGFR) and c-Met, or intracellular receptors such as androgen receptor(AR) and estrogen receptor(ER), by drugs like erlotinib,sunitinib and cabozantinib, or enzalutamide and tomoxifen? Question 54. How can we robustly identify the candidate causal event of somatic genome alteration(SGA) by using computational approach? Question 55. How can we systematically reveal the immune evasion mechanism exploited by each tumor and utilize such information to guide targeted therapy to restore immune sensitivity? Question 56. Can the nasopharyngeal carcinoma(NPC) patients with sarcomatoid carcinoma(SC) subtype benefit from more specific targeted therapy?

The 150 most important questions in cancer research and clinical oncology series:Questions 25–30

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 immunotargeting 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?

The 150 most important questions in cancer research and clinical oncology series:questions 76-85

Since the beginning of 2017, Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology to promote cancer research and accelerate collaborations. In this article, 10 questions are presented as followed. Question 76. How to develop effective therapeutics for cancer cachexia? Question 77.How can we develop preclinical animal models to recapitulate clinical situations of cancer patients for more effective anti-cancer drug development? Question 78. How can we develop novel effective therapeutics for pancreatic cancer and hepatocellular carcinoma? Question 79. What are the true beneficial mechanisms of antiangiogenic therapy in cancer patients? Question 80. How to approach the complex mechanisms of interplay among various cellular and molecular components in the tumor microenvironment? Question 81. Can tissue oxygenation improve the efficacy of conventional chemotherapy on cancer? Question 82. Can tissue oxygenation improve the efficacy of radiotherapy on digestive system tumors including liver cancer? Question 83. Can we integrate metabolic priming into multimodal management of liver cancer? Question 84. Has the limit of anti-androgen strategy in prostate cancer treatment been reached by the new generation of anti-androgen drugs? Question 85. Can we identify individuals with early-stage cancers via analyzing their clinical and non-clinical information collected from social media, shopping history, and clinical, pathological, and molecular traces?

The 150 most important questions in cancer research and clinical oncology series:questions 57-66

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?

The 150 most important questionsin cancer research and clinical oncology series:questions 40-49

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 papillomavirusinfected 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?

The 150 most important questions in cancer research and clinical oncology series:questions 67–75

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 e ective to kill cancer stem cells? Question 73. Is there any diversity among di erent types of cancer in terms of sensitivity to heavy ion beam radiotherapy? Question 74. Can targeted alpha-particle therapy augment the e ect of carbon ion radiotherapy on malignancies? Question 75. How does chromosomal instability drive tumor progression?

The 150 most important questions in cancer research and clinical oncology series: questions 86-93

Since the beginning of 2017,Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology,which spark diverse thoughts,interesting communications,and potential collabora-tions among researchers all over the world.In this article,8 more questions are presented as follows.Question 86.In which circumstances is good supportive care associated with a survival advantage in patients with cancer?Question 87.Can we develop animal models to mimic immunotherapy response of cancer patients?Question 88.What are the mechanisms underlying hepatitis B virus-associated non-hepatocellular cancers?Question 89.Can we more pre-cisely target tumor metabolism by identifying individual patients who would benefit from the treatment?Question 90.What type of cranial irradiation-based prophylactic therapy combination can dramatically improve the survival of patients with extensive small-cell lung cancer?Question 91.How can postoperative radiotherapy prolong overall survival of the patients with resected pIIIA-N2 non-small cell lung cancer?Question 92.What are the key molecular events that drive oral leukoplakia or erythroplakia into oral cancer?Question 93.How could we track the chemothera-peutics-driven evolution of tumor genome in non-small cell lung cancer for more effective treatment?