Question ID: Oct 9-1
Submitted by: October 9, 2010 Provocative Questions Workshop - Submitted to the website
January 9, 2011
Why are some disseminated cancers cured by chemotherapy alone?
Background: Although chemotherapy is very effective only very occasionally and turning cancer into a chronic, asymptomatic condition is often stated to be a desired outcome, it is well established that certain disseminated cancers can be completely cured with chemotherapy. These include solid tumors (testicular carcinoma, choriocarcinoma, and Wilms’ tumor) and hematological malignancies (ALL, Burkitt’s lymphoma, and diffuse large B-cell lymphoma).
Feasibility: New methods are available for studying the biology of these “curable” cancers and for exploring the mechanisms by which the effective drugs work.
Implications of success: If we could identify the properties of cancers that render them susceptible to eradication by chemotherapy, we might better understand how certain therapies work, contemplate converting relatively insensitive tumors to highly sensitive ones, or develop new approaches to the treatment of intransigent malignancies.
Average Score: 5.0
 (1 evaluation)Provocativeness - 5.0
Novelty - 5.0
Public Health Significance - 5.0
Feasibility - 5.0
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Comments
Submitted By Richmond Prehn
Hypothesis: If all or many cancers are dependent on a stimulatory level of immune reactants, therapies that reduce the immune response sufficiently might be curative http://www.tbiomed.com/content/7/1/4.
Submitted By Michael Lerman
This question is highly important.
Indeed, high-dose cisplatin-based chemotherapy represents a curative option for patients with testicular germ cell tumors including seminoma and nonseminomas, namely embryonal carcinoma, yolk-sac tumor, teratoma, and choriocarcinoma.
The curative effect is most likely due to large growth fractions in these solid and hematological tumors and probably high expression of protein target(s) of cisplatin.
At least one such protein target of cisplatin was identified in species ranging from yeast to humans. These predictions could be easily verified. If true then relatively insensitive tumors should be first converted into rapidly growing variants and subsequently cured with cisplatin.
Michael I. Lerman
Submitted By Olivera Finn
The importance of this question depends on what sort of research will be considered important to fund. If we prioritize research on the tumor cell and forget about the host response, we might miss the answer. This has in part been happening in many studies over many years that attempted to find the most effective chemotherapy by testing its effects on the growth of a xenograft in an immunocompromized mouse.
