Provocative questions in cancer research:
A decade later
Nearly a decade ago, a list of
provocative questions was discussed. Highlighted pointers included cancer and
ageing, obesity, evolution and statistics. A decade later, we review the
progress made in guiding government bodies, research institutes and other
organisation towards a more channelled use of funds towards a commonly
understood barrier in cancer research and therapy. Whilst the website of the
national cancer institute (https://provocativequestions.cancer.gov/) continues
to be a fantastic forum to view the challenges of the year, there are still
many hurdles to cross and every year that researchers and investigators find a
solution to one, two or more questions arise. As a result, we must strive to
keep the community of researchers up to date on the challenges ahead.
A topic that must be understood
first and foremost is that the hallmarks of cancer that are understood to date
are limited by our perception of the influencing factors in tumourigenesis, At
present, there are 16 different hallmarks of cancer; namely, (1)
Selective growth and proliferation advantage, (2) altered stress response
favouring overall survival, (3) DNA repair, (4) Apoptosis, (5) Autophagy, (6)
Senescense, (7) Vascularization, (8) Angiogenesis, (9) Non-angiogenic tumour
vascularization, (10) Invasion and circulation, (11) Intravasation and
circulation, (12) Extravasation and organ prediction, (13) Micro-metastasis,
dormancy and colonization, (14) metabolic reprogramming, (15) TME modulation,
(16) Immune modulation [PMID:
228560055]. One crucial bit of information realised as a result of
categorical segregation of the different hallmarks, is that all the hallmarks
of cancer are somehow interlinked in their feedback response or their
initiations cycles. This being either in part or wholly dependant on a
variety of factors, from genetic, metabolic, hormonal, environmental or simply
induced by oxidative stress.
As a mere freshman in the race to
contribute in the fight against cancer, I do find myself overwhelmed by the
abundance of data and information on our common adversary that resides dormant
inside us all. Before I dwell further onto the provocative questions (PQs) of
our time, let me dwell a bit into the history and the PQs of the past; most
notably, the ones from the 2018-2020 batch of research questions.
Below I have presented my selection
of a few of the ones I found most interesting in the collection of PQs
published from 2018-2019:
(1) What molecular mechanisms influence disease penetrance in individuals who inherit a cancer susceptibility gene?
(2) How does mitochondrial heterogeneity influence tumourigenesis or progression?
(3) Developing tools to directly change expression for function of multiple genes of interest and use these tools to study the range of changes important for human cancer?
(4) What are cancer specific subcellular pathogenomic structures? How do they form and what is their function? Are they a novel therapeutic target?
(5) What are the predictive biomarkers of immune-related early onset of checkpoint inhibitions?
(6) Through what mechanisms do diet and nutritional interventions affect the response to cancer treatment?
These are a few of the many research questions and should not be confused as specific topics to be used as a research topic. This being due to a requirement for a large number of answers to a larger collective of variables and questions. The provision of which would make the life of a researcher and his principal investigator (PI) so much easier. Surely, they of all people would appreciate help in guiding them to the right questions. A wrong question can lead you down the wrong path and a greater loss of time. Time that is otherwise crucial and a researcher’s worst enemy.
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