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Purpose: For many cancers, adolescents and young adults (AYA) have worse outcomes than for children and adults. Many factors may contribute to the AYA survival gap, including differences in biology, therapeutic intent, and adherence to therapy. It has been observed that male AYAs have poorer outcomes than females. The purpose of this work was to test the proposition that gender-related pharmacologic factors may account for a component of the AYA survival gap.Patients and Methods: A prospective, multi-institutional pharmacologic study of 79 patients in total with chemosensitive cancers (Ewing sarcoma, osteosarcoma and Hodgkin lymphoma) was conducted, with conventional doxorubicin treatment. Pharmacokinetic data of 13 children, 40 AYAs and 13 adults were valid for analysis. Population pharmacokinetics models were developed for doxorubicin and its metabolite doxorubicinol based on the data created in this study. Consequently, model-based analysis was conducted to investigate the relevant topics.Results: The clearance of doxorubicinol (normalized to body surface area), the main active metabolite of doxorubicin, appears faster in male AYAs than female (p = 0.04, 95% CI 0.1-3.9 L/h). The exposure of doxorubicinol (normalized to dose) is lower in male AYA than female (p = 0.03, 95% CI - 0.005 to - 0.0002 h/L). These might be correlated to the observed difference on nadir neutrophil count between male AYA and female (p = 0.027, 95% CI 0.09-1.4).Conclusion: Gender-related differences in doxorubicin pharmacology may account for worse outcomes for male AYAs with chemosensitive cancers compared to females. These findings may reduce the AYA survival gap compared to other age groups. [ABSTRACT FROM AUTHOR]

The preparative parameters have been optimized for NiO film formation in fabricated Spray Pyrolysis System using pneumatic air pressure driven aerosol formation. The structural studies by X-ray diffractometer (XRD) have been carried out to investigate crystallographic features. It was revealed that NiO crystallizes in cubic bunsenite structure. The optical band gap for direct transitions was found to be equal to 3.67 eV. Field Emission Scanning Electron Micrographs (FESEM) have been employed to study morphological aspects of the prepared films. The elemental depth profiles of film contents have been obtained Auger Electron Spectroscopic (AES) studies. [ABSTRACT FROM AUTHOR]

Background:Preoperative radiotherapy (RT) is commonly used to treat localised soft-tissue sarcomas (STS). Hypoxia is an important determinant of radioresistance. Whether antiangiogenic therapy can 'normalise' tumour vasculature, thereby improving oxygenation, remains unknown.Methods:Two cohorts were prospectively enrolled. Cohort A evaluated the implications of hypoxia in STS, using the hypoxic tracer 18F-azomycin arabinoside (FAZA-PET). In cohort B, sunitinib was added to preoperative RT in a dose-finding phase 1b/2 design.Results:In cohort A, 13 out of 23 tumours were hypoxic (FAZA-PET), correlating with metabolic activity (r2=0.85; P<0.001). Two-year progression-free (PFS) and overall (OS) survival were 61% (95% CI: 0.44-0.84) and 87% (95% CI: 0.74-1.00), respectively. Hypoxia was associated with radioresistance (P=0.012), higher local recurrence (Hazard ratio (HR): 10.2; P=0.02), PFS (HR: 8.4; P=0.02), and OS (HR: 41.4; P<0.04). In Cohort B, seven patients received sunitinib at dose level (DL): 0 (50 mg per day for 2 weeks before RT; 25 mg per day during RT) and two patients received DL: −1 (37.5 mg per day for entire period). Dose-limiting toxicities were observed in 4 out of 7 patients at DL 0 and 2 out of 2 patients at DL −1, resulting in premature study closure. Although there was no difference in PFS or OS, patients receiving sunitinib had higher local failure (HR: 8.1; P=0.004).Conclusion:In STS, hypoxia is associated with adverse outcomes. The combination of sunitinib with preoperative RT resulted in unacceptable toxicities, and higher local relapse rates. [ABSTRACT FROM AUTHOR]

Biallelic protein-truncating mutations in the adenomatous polyposis coli (APC) gene are prevalent in sporadic colorectal cancer (CRC). Mutations may not be fully inactivating, instead producing WNT/β-catenin signalling levels 'just-right' for tumourigenesis. However, the spectrum of optimal APC genotypes accounting for both hits, and the influence of clinicopathological features on genotype selection remain undefined. We analysed 630 sporadic CRCs for APC mutations and loss of heterozygosity (LOH) using sequencing and single-nucleotide polymorphism microarrays, respectively. Truncating APC mutations and/or LOH were detected in 75% of CRCs. Most truncating mutations occurred within a mutation cluster region (MCR; codons 1282-1581) leaving 1-3 intact 20 amino-acid repeats (20AARs) and abolishing all Ser-Ala-Met-Pro (SAMP) repeats. Cancers commonly had one MCR mutation plus either LOH or another mutation 5′ to the MCR. LOH was associated with mutations leaving 1 intact 20AAR. MCR mutations leaving 1 vs 2-3 intact 20AARs were associated with 5′ mutations disrupting or leaving intact the armadillo-repeat domain, respectively. Cancers with three hits had an over-representation of mutations upstream of codon 184, in the alternatively spliced region of exon 9, and 3′ to the MCR. Microsatellite unstable cancers showed hyper-mutation at MCR mono- and di-nucleotide repeats, leaving 2-3 intact 20AARs. Proximal and distal cancers exhibited different preferred APC genotypes, leaving a total of 2 or 3 and 0 to 2 intact 20AARs, respectively. In conclusion, APC genotypes in sporadic CRCs demonstrate 'fine-tuned' interdependence of hits by type and location, consistent with selection for particular residual levels of WNT/β-catenin signalling, with different 'optimal' thresholds for proximal and distal cancers. [ABSTRACT FROM AUTHOR]

The Polycap (polypill; aspirin [acetylsalicylic acid], ramipril, simvastatin, atenolol, and hydrochlorothiazide) was found to be safe and effective for reducing multiple cardiovascular risk factors in The Indian Polycap Study (TIPS). We evaluated the bioavailability of each ingredient of the Polycap and determined any drug-drug interactions relative to single component reference preparations. The bioavailability of the ingredients of the Polycap (T; test) when formulated as a single capsule was compared with that of identical capsules with each of its ingredients administered separately (R; reference) in a five-arm, randomized, single-dose, two-period, two-treatment, two-sequence, crossover trial with at least a 2-week washout period in a total of 195 healthy volunteers. Plasma concentrations of each drug and, where applicable, its active metabolite were measured using validated liquid chromatography-tandem mass spectrometry and ultra-performance liquid chromatography. Mean pharmacokinetic parameters and their standard deviations were computed for each analyte. Comparative bioavailability was computed and no drug-drug interactions and no difference in comparative bioavailability were concluded for each ingredient based on point estimates of the T/R ratio of the geometric means falling within 80-125% for peak plasma concentration (C(max)), area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC(t)), and AUC from time zero to infinity (AUC(infinity)). The T/R ratio for C(max), AUC(t) and AUC(infinity) was within 80-125% for atenolol, hydrochlorothiazide, ramipril, ramiprilat and dose-normalized salicylic acid. However, for simvastatin, the T/R point estimates for C(max), AUC(t) and AUC(infinity) for Ln-transformed data were significantly lower ( approximately 3-4%) than the lower bound of 80%. For its active metabolite, simvastatin acid, these estimates were significantly higher ( approximately 25-35%) than the higher bound of 125%. Thus, the increased bioavailability of active simvastatin acid appeared to compensate for the loss of bioavailability of simvastatin. The Polycap was found to be effective and safe in the previously published TIPS trial. The present study in healthy volunteers establishes that Polycap is safe (no serious adverse events) and well tolerated, and that there is no indication of pharmacokinetic drug-drug interactions for any of the ingredients, with their bioavailabilities being well preserved. [ABSTRACT FROM AUTHOR]

Copyright of Bulletin of Engineering Geology & the Environment is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

During the total solar eclipse of 11 June, 1983, an imaging dual-channel Fabry-Pérot interferometer was used to obtain line profiles simultaneously in the green λ5303 Å [Fe xiv] and the red λ6374 Å [Fe x] coronal lines at various positions in the corona. Extensive microdensitometry followed by multi-Gaussian curve-fitting analysis has resulted in the determination of coronal temperatures and velocity separations between different pockets of coronal gas in the line of sight over a large extent of the corona. Fewer high temperature zones are to be found in the corona of 1983 compared with our similar green-line measurements of the solar maximum corona of 1980. The data are consistent with a temperature maximum occurring at 1.2 R, as found at the 1980 eclipse, but our new data are insufficient to observe farther out than this radius and so determine the position of a maximum. The velocity field in the corona at the 1983 eclipse is less structured compared with that at the 1980 eclipse and is mainly confined to the zone 20-30km s. [ABSTRACT FROM AUTHOR]

Addition of 1,8-diaminonaphthalene 1 to dimethylacetylene dicarboxylate (DMAD) leads to the perimidine 4a and the naphthodiazepine 3a. A similar reaction with the diethyl ester (DEAD) gave rise to 3b and 4b. The latter product has been incorrectly formulated as naphthodiazepine 2b in the literature. 1,8-Dihydroxynaphthalene 8 and DMAD gives rise to the naphthodioxane 9, which is hydrolysed to the diacid 11. 8-Hydroxy-1,2,3,4-tetrahydroquinoline ( 14) and acetylenic esters form pyridobenzoxazines 15, which exist as equilibrium mixture of 15 and 16 in solution. The ethyl ester is hydrogenated to the dihydroderivative 18b.H and more particularlyC NMR spectra are used to assign structures to various products. [ABSTRACT FROM AUTHOR]

The excitation mechanism of the coronal green line in various coronal regions is studied. The line-to-continuum intensity ratio is calculated using the model electron density values given by Newkirk (1961) and is compared with the observed values. Reasonably good agreement is found between the model calculations and observed values. The model calculations show that collisional excitation is more important in the innermost regions while radiative contribution progressively increases towards outer regions. The individual contributions depend strongly on the activity of the particular coronal region. An increased contribution from collisional excitation is seen in coronal active regions owing to the large electron density. A contour map of the line-to-continuum intensity ratio as derived from the observations, is plotted. At 1.10 R⊙ the value is about 80 in active regions, 30-40 in coronal streamers, while it is less than 10 in polar regions. [ABSTRACT FROM AUTHOR]

During the anaerobic biodegradation of effluent from a dimethyl terephthalate (DMT) manufacturing plant, reduction in chemical oxygen demand (COD) degradation and biogas formation was observed after the waste-water concentration exceeded 25% of added feed COD. This condition reverted back to normal after 25-30 days when the DMT waste-water concentration in the feed was brought down to a non-toxic level. However, the above effects were observed only after the concentration of DMT waste-water reached more than 75% of added feed COD when biomass support particles (BSP) were augmented to the system. In the BSP system, a biomass concentration of up to 7000 mg/l was retained and the sludge retention time increased to > 200 days compared to 2200 mg/l and 8-10 days, respectively, in the system without BSP (control). Formaldehyde in the waste-water was found to be responsible for the observed toxicity. The BSP system was found to resist formaldehyde toxicity of up to 375 mg/l as against 125 mg/l in the control system. Moreover, the BSP system recovered from the toxicity much faster (15 days) than the control (25-30 days). The advantages of the BSP system in anaerobic treatment of DMT waste-water are discussed. [ABSTRACT FROM AUTHOR]

Slop oil, i.e. waste oil from a petrochemical complex, contains at least 240 hydrocarbon components, of which 54% are from C to C and the rest from C to C. Of 22 isolated bacterial cultures that were able to degrade slop oil, seven could each degrade about 40% of the slop oil, and a mixture of all seven could degrade ≤50% in liquid medium. Bioaugmentation of soil contaminated with slop oil with the mixed bacterial culture gave up to 70% degradation of slop oil after 30 days. This compares with 40% degradation without bioaugmentation. Bioaugmentation led to a significant increase in counts of bacteria able to degrade slop oil. Wheat sown on bioaugmented soil germinated and grew better than on non-augmented soil and led to increased degradation of slop oil (up to 80%). This indicates the potential of mixed culture for bioremediation. [ABSTRACT FROM AUTHOR]

During our screening program for hydrocarbon-degrading microorganisms Pseudomonas fluorescens was isolated that grew on gasoline as the sole source of carbon and energy. During growth on gasoline it produced proline and tryptophan. Among the nitrogen salts tested, ammonium sodium hydrogen orthophosphate supported maximum amino acid production and growth. By optimizing the medium components a two-fold increase in proline and tryptophan production was achieved. [ABSTRACT FROM AUTHOR]

Simultaneous reduction in alkaloid yield and level of phosphatases by high concentrations of phosphate was observed in Claviceps sp. SD-58. Tryptophan-induced culture showed an increase in alkaloid yield and the level of phosphatases. Phosphate caused repression of both acid phosphatase (isoenzyme I) and alkaline phosphatase (isoenzymes III and V). [ABSTRACT FROM AUTHOR]

Alkaloid biogenesis in Claviceps sp. SD-58 was found to be associated with low growth and reduced consumption of sucrose and mannitol. The activities of glucose-6-phosphate dehydrogenase and aldolase increased up to 9 d of the fermentation cycle and then declined. A close parallel between the operation of pentose phosphate and glycolytic pathways and tryptophan content was demonstrated. An inverse relation between the operation of citric acid and glyoxylate cycles and the ability of the cells to synthesize alkaloids was noted. The role of carbon metabolic pathways during fermentative production of alkaloids is discussed. [ABSTRACT FROM AUTHOR]

The proposed method includes primary and secondary treatments. Of the various disinfectants tested, 1-propanol and 1-butanol as a primary treatment and phenol, resorcinol, HgCl or NaCl as a secondary treatment completely eliminated the contamination hazard. 1-Butanol and phenol were not useful disinfectants since they inhibited the growth of C. fusiformis along with the other contaminants. Primary and secondary treatment of sclerotia with 1-propanol and resorcinol, respectively, produced the maximum of stable cultures. Out of 120 cultures tested, 5 cultures demonstrated an appreciable yield of alkaloids under submerged cultural conditions. [ABSTRACT FROM AUTHOR]

Biotin deficiency in Aspergillus nidulans resulted in a 70 % increase of the protein content and increased levels of free and bound aspartate, glutamate, serine, leucine and methionine. Likewise, the activities of NADP glutamate dehydrogenase, NAD glutamate dehydrogenase, aspartate aminotransferase and alanine aminotransferase were significantly increased. The total UNA content increased while the DNA content was unaffected. The rRNA/tRNA ratio remained higher in biotin-deficient cells. Supplementation of glutamate, aspartate, serine, leucine and methionine to the culture medium raised the rRNA/tRNA ratio, and the difference observed in the qualitative and the quantitative patterns of protein and dry cell mass between normal and biotin-deficient cultures was abolished. [ABSTRACT FROM AUTHOR]

Biotin deficiently resulted in an increased growth rate of Aspergillus nidulans. The activities of hexokinase and aldolase were not much changed during the growth cycle, but activities of glucose-6-phosphate dehydrogenase and NADP-linked glutamate dehydrogenase increased significantly during the exponential phase. This change was remarkable during biotin deficiency. In contrast to the higher growth rate and respiration rate during biotin deficiency the activities of NAD(P)H oxidoreductases were low. An inverse relationship between the activity of tyrosinase and melanin content was observed. A role of the DOPA-DOPA-quinone system in maintaining culture growth is suggested. [ABSTRACT FROM AUTHOR]

Copyright of Microchimica Acta is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Thirty cases of neurogenic tumours of the head and neck have been presented. The pathology, clinical features and their management is discussed. They are benign tumours and grow slowly over a period of years. They are resistant to irradiation and not radiocurable. The majority of tumours can be removed by enucleation safely and adequately by surgical procedures. Recurrence is rare even if a portion of the capsule cannot be excised completely. Malignant changes are rarely seen in our 2 cases. Small parapharyngeal tumours can be removed safely and effectively by a transoral approach. But large para pharyngeal and laryngeal tumours can be removed best via external cervical approach. [ABSTRACT FROM AUTHOR]

The cometary images taken on 1986 January 8.590 and 8.638 UT ( R-0.9 AU, δ ~ 1.29 AU) at Gurushikhar, Mt. Abu, India (24 °39′ N, 72 °43′ E alt: 1700 m) show distinct condensation region in the tail direction. The size of the condensation region is 4 × 10 km. The condensation region showed up strongly in the blue emission, implying the abundance of CO. It was inferred to be moving with a velocity of 37 ± 3 km/s relative to the comet at a distance of 2.3 × 10 km from the nucleus in the tailward direction. The analysis show that the condensation was a result of rapid ionization mechanism, with a time scale of \~10 to 10 sec. The most probable mechanism for producing the ionization region was found to be the discharge of cross tail electric current passing through the neutral sheet in the near nucleus region followed by an outburst observed in IR wavelengths at 8.1 UT. It was accelerated by J × B drift at a rate of ~24 cm/sec to the position observed by us. This feature, most probably is the precursor of the first dramatic Disconnection Event (DE) observed in Halley's Comet at Jan.10.375 UT. This supports the conjecture that the tail features originate in the coma with a velocity of ~20-40 km/s. [ABSTRACT FROM AUTHOR]

The observation of [OI] 6300 » emission in the coma of Halley's comet 1982i, using the imaging Fabry-Pérot spectrometer, was carried out from Gurushikhar (24‡39′N, 72‡43′E, 1700m altitude), Mt. Abu, India on March 15, 1986 ( R = 0.90 AU, δ = 0.96 AU). The analysis of the interferogram show the absence of the differential velocity of neutral oxygen above 5 km s. [ABSTRACT FROM AUTHOR]

During the occultation of a star by the inner coma region of a comet, specific forward-scattering effects could be observable if submillimeter size particles contribute significantly to the net extinction of star light. In this paper we investigate the possibility of detecting the signature of such particles by observing the dependence of extinction on the angular size of the acceptance aperture used at the focal plane of the telescope. Calculations based on a simple model assuming spherically-symmetric and homogeneous coma are presented. [ABSTRACT FROM AUTHOR]

Gastrointestinal stromal tumors lacking mutations in KIT or PDGFRα are known as wild type (WT) and are less responsive to imatinib. These WT tumors are hypothesized to be dependent on signaling through the insulin-like growth factor 1 receptor (IGF-1R). We report the case of a 29-year-old woman with neurofibromatosis type 1-associated WT GIST treated with an anti-IGF-1R monoclonal antibody. Treatment was ineffective, and the potential basis for lack of response is discussed in the context of IGF-1R expression levels measured within this patients' primary tumor. We suggest that future clinical trials of anti-IGF-1R therapies prospectively determine tumor IGF-1R expression levels for correlation with response to treatment. [ABSTRACT FROM AUTHOR]

Copyright of Experientia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Six cases of achalasia cardia in children are reported. The aetiological aspects are discussed, and evidence for absence of Auerbach's plexus is presented. The value and results of the modified Heller's operative procedure are discussed. [ABSTRACT FROM AUTHOR]

Tenosynovial giant cell tumors (TGCT), are rare colony stimulating factor-1(CSF-1)-driven proliferative disorders affecting joints. Diffuse-type TGCT often causes significant morbidity due to local recurrences necessitating multiple surgeries. Imatinib mesylate (IM) blocks the CSF-1 receptor. This study investigated the long term effects of IM in TGCT. We conducted an international multi-institutional retrospective study to assess the activity of IM: data was collected anonymously from individual patients with locally advanced, recurrent or metastatic TGCT. Sixty-two patients from 12 institutions across Europe, Australia and the United States were identified. Four patients with metastatic TGCT progressed rapidly on IM and were excluded for further analyses. Seventeen of 58 evaluable patients achieved complete response (CR) or partial response (PR). One- and five-year progression-free survival rates were 71% and 48%, respectively. Thirty-eight (66%) patients discontinued IM after a median of 7 (range 1–80) months. Reported adverse events in 45 (78%) patients were among other edema (48%) and fatigue (50%), mostly grade 1–2 (89%). Five patients experienced grade 3–4 toxicities. This study confirms, with additional follow-up, the efficacy of IM in TGCT. In responding cases we confirmed prolonged IM activity on TGCT symptoms even after discontinuation, but with high rates of treatment interruption and additional treatments. [ABSTRACT FROM AUTHOR]

Etoposide is commonly used in a variety of malignancies. A well known but rare toxicity are hypersensitivity reactions, usually manifested by chest discomfort, dyspnoea, bronchospasm and hypotension. We report the details of a patient who developed hypersensitivity reactions to intravenous etoposide, but subsequently tolerated the administration of intravenous etoposide phosphate with no sequelae. [ABSTRACT FROM AUTHOR]

Phosphate uptake in Claviceps sp. strain SD-58 was found to be linear for 20 min, proportional to cell density in mg/ml, energy dependent, and taking place against a concentration gradient with a K value of 45.45×10 M. Osmotic shock treatment to the cell caused a reduction in phosphate uptake associated with the release of binding protein. Partial restoration of uptake was observed on incubation of osmotically shocked cells with shock fluid. The results are discussed with reference to the effect of phosphate on alkaloid synthesis in Claviceps sp. strain SD-58. [ABSTRACT FROM AUTHOR]

The ammonia uptake in A. nidulans was found to be linear for about 20 min, and was proportional up to 1.5 mg/ml dry cell density. The transport of ammonia does not involve energy. Normal and biotin deficient A. nidulans showed an identical K-values of 10.26×10 M ammonia for uptake. The uptake of ammonium ion has been shown to be regulated by the intracellular concentration of ammonia. [ABSTRACT FROM AUTHOR]

Pyruvate and acetate inhibited the uptake of glucose by Aspergillus nidulans; although there were significant variations in glucose uptake rate, the intracellular concentration of acetate was almost identical in biotin-supplemented, normal and deficient cells. The in vitro activity of glucose-binding protein was not affected by biotin, avidin, acetate or acetyl-CoA. [ABSTRACT FROM AUTHOR]

Biotin deficiency in Aspergillus nidulans has been found to increase the uptake of ammonium ions, associated with a marked increase in the activity of NADP-linked glutamate dehydrogenase, which is found to be the major route of ammonia assimilation in this culture. The results obtained are discussed with respect to the growth of Aspergillus nidulans during biotin deficiency. [ABSTRACT FROM AUTHOR]

An interesting, rare ulcerative lesion- a midfacial granuloma was encountered by us. It was histologically diagnosed as a case of histiocytic lymphoma. The same is being presented here with a brief review of the recent trends in the literature on the subject of the histogenesis of idiopathic midfacial pleomorphic granuloma. [ABSTRACT FROM AUTHOR]

Embryonal Rhabdomyosarcoma is a relatively uncommon tumour of head and neck region. It is more common in children. In this paper two cases of Embryonal Rhabdomyosarcoma presenting in middle ear and mastoid region are reported. [ABSTRACT FROM AUTHOR]

This single-arm phase II non-randomised trial (ACTRN12619001265167) evaluated trastuzumab emtansine in solid cancers with HER2 amplification or mutation detected by comprehensive genomic profiling. The primary objective was objective response (OR), while secondary objectives included the time to progression (TTP) on study to TTP on prior therapy ratio, progression-free survival (PFS) and overall survival (OS). The cohort included 16 tumours with HER2 mutations (group 1) and 16 with HER2 amplification (group 2). After 17 months median follow-up, ORs occurred in 19% of group 1 (1 salivary gland carcinoma (SGC), 2 lung cancers) and 25% of group 2 (3 SGCs, 1 uterine carcinoma). Fourteen of 29 TTP-evaluable patients achieved a TTP ratio ≥1.3, including 10 without an OR. Median PFS and OS were 4.5 (95% CI 2.1-7.0) and 18.2 months (95% CI 8.1-not reached) respectively. Trastuzumab emtansine showed modest ORs and a favourable change in disease trajectory in select HER2-altered solid cancers., (© 2024. The Author(s).)

While several resources exist that interpret therapeutic significance of genomic alterations in cancer, many regional real-world issues limit access to drugs. There is a need for a pragmatic, evidence-based, context-adapted tool to guide clinical management based on molecular biomarkers. To this end, we have structured a compendium of approved and experimental therapies with associated biomarkers following a survey of drug regulatory databases, existing knowledge bases, and published literature. Each biomarker-disease-therapy triplet was categorised using a tiering system reflective of key therapeutic considerations: approved and reimbursed therapies with respect to a jurisdiction (Tier 1), evidence of efficacy or approval in another jurisdiction (Tier 2), evidence of antitumour activity (Tier 3), and plausible biological rationale (Tier 4). Two resistance categories were defined: lack of efficacy (Tier R1) or antitumor activity (Tier R2). Based on this framework, we curated a digital resource focused on drugs relevant in the Australian healthcare system (TOPOGRAPH: Therapy Oriented Precision Oncology Guidelines for Recommending Anticancer Pharmaceuticals). As of November 2020, TOPOGRAPH comprised 2810 biomarker-disease-therapy triplets in 989 expert-appraised entries, including 373 therapies, 199 biomarkers, and 106 cancer types. In the 345 therapies catalogued, 84 (24%) and 65 (19%) were designated Tiers 1 and 2, respectively, while 271 (79%) therapies were supported by preclinical studies, early clinical trials, retrospective studies, or case series (Tiers 3 and 4). A companion algorithm was also developed to support rational, context-appropriate treatment selection informed by molecular biomarkers. This framework can be readily adapted to build similar resources in other jurisdictions to support therapeutic decision-making.