Below is a piece of a recent nice article proposing a broad-spectrum integrative approach for cancer prevention and treatment. I find it interesting specifically because the article is suggesting a large list of drugs and supplements that are easy to access while addressing multiple anti cancer mechanisms.
The article is entitled: Designing a broad-spectrum integrative approach for cancer prevention and treatment http://www.sciencedirect.com/science/article/pii/S1044579X15000887
Abstract: Targeted therapies and the consequent adoption of €œpersonalized€ oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity €œbroad-spectrum€ therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment. Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered.
Table S3. Approaches listed by hallmark for all hallmarks. Cross-validations are shown for each approach-hallmark interaction.
(AN, angiogenesis; AP, resistance to apoptosis; DM, dysregulated metabolism; EAG, evasion of anti-growth signaling; GI, genomic instability; IE, immune evasion; RI, replicative immortality; SPS, sustained proliferative signaling; TIM tissue invasion and metastasis; TME, tumor microenviroment; TPI, tumor promoting inflammation.)
Hall-marks | Approaches | Genomic Instability (GI) | Sustained Prolifera-tive Signaling (SPS) | Tumor-promoting Inflamma-tion (TPI) | Evasion of Anti-growth Signaling (EAG) | Resis-tance to Apoptosis (AP) | Replica-tive Im-mortality (RI) | Dysregu-lated Meta-bolism (DM) | Immune System Evasion (IE) | Angio-genesis (AN) | Tissue Invasion and Metasta-sis (TIM) | Tumor Micro-environ-ment (TME) |
ANa | Curcumin | + | + | + | + | + | + | + | + | + | + | + |
AN | EGCG | + | + | + | + | + | + | + | + | + | + | + |
AN | Enterolactone | 0 | + | + | + | + | 0 | 0 | 0 | + | + | + |
AN | Kaempferol | 0 | 0 | + | + | + | 0 | + | 0 | + | + | + |
AN | Melatonin | + | + | 0 | + | + | + | + | + | + | + | + |
AN | Oleanoic acid | + | 0 | + | + | + | + | + | + | + | + | + |
AN | Resveratrol | + | + | + | + | + | + | + | +/- | +/- | + | + |
AN | Silibinin | + | + | + | + | + | + | + | + | + | + | + |
AN | Tripterine | 0 | 0 | 0 | + | + | 0 | 0 | 0 | + | + | + |
AN | Withaferin A | 0 | + | + | + | + | 0 | + | + | + | + | + |
AP | EGCG | + | + | + | + | + | + | + | + | + | + | + |
AP | Gossypol | 0 | + | + | + | + | + | + | 0 | + | + | + |
AP | Selinexor | 0 | 0 | 0 | 0 | + | 0 | 0 | 0 | 0 | + | + |
AP | Triptolide | 0 | + | + | + | + | + | + | – | + | + | + |
AP | UMI-77 | 0 | + | 0 | + | + | 0 | 0 | 0 | 0 | + | + |
DM | 3-bromopyruvate | 0 | + | 0 | + | + | 0 | + | 0 | + | + | + |
DM | BPTES | 0 | + | 0 | + | 0 | 0 | + | 0 | 0 | + | + |
DM | Dichloroacetate | 0 | + | + | 0 | 0 | 0 | + | + | + | + | + |
DM | FX11 | – | 0 | 0 | 0 | 0 | 0 | + | 0 | 0 | 0 | + |
DM | GW5074 | 0 | +/- | 0 | + | 0 | 0 | + | 0 | 0 | + | 0 |
DM | Hexachlorophene | + | + | 0 | + | + | 0 | + | 0 | 0 | + | 0 |
DM | Metformin | + | +/- | + | + | + | + | + | + | + | + | + |
DM | PK15 | + | + | 0 | + | + | 0 | + | 0 | 0 | + | 0 |
DM | Resveratrol | + | + | + | + | + | + | + | +/- | +/- | + | + |
DM | TEPP-46 | 0 | 0 | + | 0 | 0 | 0 | + | 0 | 0 | 0 | + |
EAG | Curcumin | + | + | + | + | + | + | + | + | + | + | + |
EAG | Deguelin | 0 | + | + | + | + | 0 | 0 | 0 | + | + | + |
EAG | EGCG | + | + | + | + | + | + | + | + | + | + | + |
EAG | Genistein | + | +/- | +/- | +/- | + | + | +/- | +/- | + | + | + |
EAG | Luteolin | + | + | + | + | + | 0 | + | 0 | + | + | + |
EAG | Resveratrol | + | + | + | + | + | + | + | +/- | +/- | + | + |
EAG | Withaferin A | 0 | + | + | + | + | 0 | + | + | + | + | + |
GI | Carotenoids | + | + | + | +/- | + | + | + | + | + | + | + |
GI | Isothiocyanate | + | + | + | + | + | + | + | 0 | + | + | + |
GI | PARP inhibitor | + | + | + | + | + | + | 0 | 0 | + | + | + |
GI | Resveratrol | + | + | + | + | + | + | + | +/- | +/- | + | + |
GI | Selenium | + | +/- | – | + | + | + | 0 | 0 | +/- | + | + |
GI | Vitamin B | + | +/- | + | 0 | 0 | 0 | 0 | 0 | +/- | + | 0 |
GI | Vitamin D | + | + | + | + | + | + | 0 | + | + | + | + |
IE | Astaxanthin | 0 | + | + | + | + | 0 | 0 | + | 0 | + | + |
IE | Astragalus membranaceus polysaccharide | 0 | 0 | + | + | + | 0 | 0 | + | – | + | + |
IE | Ganoderma lucidum polysaccharide | 0 | + | + | + | + | + | 0 | + | + | + | + |
IE | HS-1793 (polyphenol resveratrol analogue) | 0 | 0 | 0 | 0 | + | 0 | 0 | + | + | + | + |
IE | Lentinus edodes polysaccharide | 0 | + | + | + | + | 0 | 0 | + | + | + | + |
IE | Trametes versicolor polysaccharide-k | 0 | 0 | 0 | + | 0 | 0 | 0 | + | 0 | 0 | + |
RI | Curcumin | + | + | + | + | + | + | + | + | + | + | + |
RI | Dinacicilib | 0 | + | 0 | + | + | + | 0 | 0 | 0 | + | + |
RI | EGCG | + | + | + | + | + | + | + | + | + | + | + |
RI | Genistein | + | +/- | +/- | +/- | + | + | +/- | +/- | + | + | + |
RI | Imetelstat | +/- | 0 | 0 | + | + | + | 0 | 0 | 0 | 0 | + |
RI | Palbociclib | 0 | + | 0 | + | + | + | 0 | 0 | 0 | – | 0 |
RI | Perillyl alcohol | + | + | + | + | + | + | + | 0 | + | + | + |
SPS | Curcumin | + | + | + | + | + | + | + | + | + | + | + |
SPS | Genistein | + | +/- | +/- | +/- | + | + | +/- | +/- | + | + | + |
SPS | Resveratrol | + | + | + | + | + | + | + | +/- | +/- | + | + |
TIM | 5,6-dihydro-4H-pyrrolo[1,2-b]-pyrrazoles | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | + | + |
TIM | Cordycepin | 0 | + | + | + | + | 0 | + | 0 | + | + | + |
TIM | Eicosapentaenoic acid | 0 | + | + | + | + | + | 0 | 0 | + | + | + |
TIM | Gamma linolenic acid | 0 | + | 0 | + | + | 0 | + | 0 | + | + | + |
TIM | Ganoderic acids | 0 | + | + | + | + | 0 | 0 | 0 | + | + | + |
TIM | Grifolin | 0 | + | 0 | + | + | 0 | + | 0 | 0 | + | + |
TIM | Pachymic acid | 0 | + | + | + | + | 0 | 0 | 0 | 0 | + | + |
TIM | Polysaccharide (G. lucidum) | 0 | +/- | + | + | + | 0 | + | + | + | + | + |
TIM | Silibinin | + | + | + | + | + | + | + | + | + | + | + |
TIM | β-(1-6)-D-glucan (A. blazei) | 0 | + | + | 0 | + | 0 | + | 0 | 0 | + | + |
TME | Berberine | + | + | 0 | + | + | + | + | – | + | + | + |
TME | Curcumin | + | + | + | + | + | + | + | + | + | + | + |
TME | Desoxyrhapontigenin | 0 | 0 | 0 | 0 | + | 0 | 0 | 0 | 0 | 0 | + |
TME | EGCG | + | + | + | + | + | + | + | + | + | + | + |
TME | Genistein | + | +/- | +/- | +/- | + | + | +/- | +/- | + | + | + |
TME | Naringenin | + | + | + | 0 | +/- | 0 | + | +/- | 0 | + | + |
TME | Onionin A | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | + |
TME | Piperine | + | + | 0 | + | + | 0 | + | – | 0 | + | + |
TME | Resveratrol | + | + | + | + | + | + | + | +/- | +/- | + | + |
TME | Zerumbone | 0 | + | 0 | 0 | + | 0 | + | + | 0 | + | + |
TPI | Anthocyanins | + | + | + | + | + | + | 0 | 0 | + | + | + |
TPI | Curcumin | + | + | + | + | + | + | + | + | + | + | + |
TPI | EGCG | + | + | + | + | + | + | + | + | + | + | + |
TPI | Genistein | + | +/- | +/- | +/- | + | + | +/- | +/- | + | + | + |
TPI | Lycopene | + | + | + | + | + | 0 | 0 | 0 | + | + | + |
TPI | Resveratrol | + | + | + | + | + | + | + | +/- | +/- | + | + |
aAN, angiogenesis; AP, resistance to apoptosis; DM, dysregulated metabolism; EAG, evasion of anti-growth signaling; GI, genomic instability; IE, immune evasion; RI, replicative immortality; SPS, sustained proliferative signaling; TIM tissue invasion and metastasis; TME, tumor microenviroment; TPI, tumor promoting inflammation.
Dear Daniel,
Just spotted your article with this useful table about treatments’ effects. Do you know what the – (minus) sign means in the table by any chance? Is it a proven non-effect (as opposed to + or 0) or is it a negative effect? I suppose it is the former.
I just wrote to Paul in the citric acid thread that there is a new finding about PARP inhibitors made sensitive to KRAS-mutant cancers if the ERK or MEK protein (kinases both I think) is inhibited: http://stm.sciencemag.org/content/9/392/eaal5148
Best,
Helga
Hi Helga,
Sorry for the delay of my answer. Good question indeed. In the article they explain it like this:
“Approaches that were found to have complementary, anti-carcinogenic actions in a particular hallmark area were were indicated with “+”, while approaches that were found to have pro-carcinogenic actions in a particular hallmark area were indicated with “-”. In instances where reports on relevant actions in other hallmarks were mixed (i.e., reports showing both anti-carcinogenic and pro-carcinogenic potential), the symbol “+/-“ was used. Finally, in instances where no literature support was found to document the relevance of an approach in a particular aspect of cancer’s biology, we documented this as “0”‘. ”
Kind regards,
Daniel