Beyond Cancer by Body Part

Why the Origin of a Tumor May Be Less Important

Regardless of where a tumor is located, its molecular composition tells doctors a lot about how the cancer may behave and what treatments will be most effective. In the not-too-distant future, we may no longer refer to cancer by its location in the body (for example, by calling it breast, colon, or lung cancer), but by the tumor’s distinct molecular composition. Doctors are already increasingly referring to certain types of cancer by the genetic mutations (changes), proteins, or other biomarkers present in the tumor or blood/tissue sample, rather than by the body part where the cancer originated. The science behind molecular profiling is still developing, but any time a physician can match your cancer’s biomarkers to a specific treatment, the better chance you’ll have of a positive outcome.

Expanding Treatment Options

A cancer’s molecular signature tells doctors a lot about what treatments may be effective – as well as which treatments may not be effective. For example, if you have lung cancer that is positive for an enzyme known as ALK, your treatment course may begin with a drug such as crizotinib (Xalkori®) or pemetrexed (Alimta®), both of which have been shown to work better in patients with ALK-positive tumors.

More simply put, if you have breast cancer, your doctor may only consider treatments that are FDA-approved for the treatment of breast cancer. However, the results in your biomarker profile report may tell your oncologist that even though you have breast cancer, your cancer cells at the molecular level behave more like those observed in people with kidney cancer. Those results may therefore convince your oncologist to select a drug traditionally used to treat kidney cancer instead of breast cancer.

Click on the images below to learn about body parts and biomarkers.

Lung Cancer

Several biomarkers are associated with Lung Cancer. These include, but are not limited to: ALK, AR, BRCA1, c-MET, COX-2, EGFR, ERCC1, KRAS, MGMT, PTEN, RRM1, TS, and TUBB3. Of these biomarkers, a mutation in the EGFR - Epidermal Growth Factor Receptor gene is usually a strong indicator. EGFR is also known as ErbB-1 or HER1.

Treatments associated with response or lack of response/resistance when a EGFR mutation is found includes: cetuximab (Erbitux®), erlotinib (Tarceva®), gefitinib (Iressa®), panitumumab (Vectibix®).

* Biomarker status (overexpressed, underexpressed, positive or negative for specific mutations, etc.) determines whether that biomarker is associated with response, lack of response or resistance to each treatment.

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Colon Cancer

Several biomarkers are associated with Colon Cancer. These include, but are not limited to: BRAF, c-Kit, EGFR, ERCC1, HER2, KRAS, PIK3CA, PTEN, TOPO2A, and TS. Of these biomarkers, a mutation in TS - thymidylate synthetase is usually a strong indicator.

51% of patients with colorectal cancers have a high TS. Treatments associated with response or lack of response/resistance when a TS mutation is found includes: lack of response to 5-fluorouracil (Adrucil®), cytarabine (Cytosar-U®), pemetrexed (Alimta®). 11% of patients with colorectal cancers are HER2 positive. Treatments associated with response or lack of response/resistance when a TS mutation is found includes: lapatinib (Tykerb®), trastuzumab (Herceptin®), doxorubicin (Adriamycin®, Rubex®), liposomal doxorubicin (Caelyx®, Myocet®), epirubicin (Ellence®). 15% of patients with colorectal cancers have a BRAF mutation. Treatments associated with response or lack of response/resistance when a TS mutation is found includes: cetuximab (Erbitux®), panitumumab (Vectibix®), vemurafenib (Zelboraf®)

* Biomarker status (overexpressed, underexpressed, positive or negative for specific mutations, etc.) determines whether that biomarker is associated with response, lack of response or resistance to each treatment.

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Bladder Cancer

Several biomarkers are associated with Bladder Cancer. These include, but are not limited to: AR. Of these biomarkers, a mutation in the AR - Androgen Receptor gene is usually a strong indicator. Androgens are “male” hormones, but the AR (androgen receptor) biomarker is commonly found in both men’s and women’s cancers. Research suggests that several types of treatments may affect AR-positive cancers including antiandrogen therapies, antiestrogen therapies and GnRH analogs.

13% of patients with bladder cancers are AR positive. Treatments associated with response or lack of response/resistance when an AR positive mutation is found includes: bicalutamide (Casodex®), flutamide (Eulexin®), goserelin (Zoladex®), leuprolide (Lupron®), abarelix (Plenaxis®), gonadorelin (Factrel®).

* Biomarker status (overexpressed, underexpressed, positive or negative for specific mutations, etc.) determines whether that biomarker is associated with response, lack of response or resistance to each treatment.

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Prostate Cancer

Several biomarkers are associated with Prostate Cancer. These include, but are not limited to: AR. As within Bladder Cancer, a mutation in the AR - Androgen Receptor gene is usually a strong indicator. Androgens are “male” hormones, but the AR (androgen receptor) biomarker is commonly found in both men’s and women’s cancers. Research suggests that several types of treatments may affect AR-positive cancers including antiandrogen therapies, antiestrogen therapies and GnRH analogs.

90% of patients with prostate cancers are AR positive. Treatments associated with response or lack of response/resistance when an AR positive mutation is found includes: bicalutamide (Casodex®), flutamide (Eulexin®), goserelin (Zoladex®), leuprolide (Lupron®), abarelix (Plenaxis®), gonadorelin (Factrel®).

* Biomarker status (overexpressed, underexpressed, positive or negative for specific mutations, etc.) determines whether that biomarker is associated with response, lack of response or resistance to each treatment.

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Breast Cancer

Several biomarkers are associated with Breast Cancer. These include, but are not limited to: AR, ER, HER2, MGMT, MRP1, PGP, PIK3CA, PR, PTEN, SPARC, TLE3, TOPO2A, and TS. The most infamous of these biomarkers, is HER2 - Human Epidermal growth factor Receptor 2, also known as HER2/neu or ErbB-2, a receptor tyrosine kinase active in cell signaling, promotes cell growth and multiplication. HER2 is a biomarker commonly associated with breast cancer. Significant percentages of patients have cancer originating in other parts of the body that also test positive for HER2. Research shows that these cancers may respond to treatments that target HER2 such as trastuzumab (Herceptin®) and lapatinib (Tykerb®).

20-30% of patients with breast cancers are HER2 positive. Research shows that these cancers may respond to treatments that target HER2 such as trastuzumab (Herceptin®) and lapatinib (Tykerb®). 32% of patients with breast cancers have a high TS. Treatments associated with response or lack of response/resistance when a TS mutation is found includes: lack of response to 5-fluorouracil (Adrucil®), cytarabine (Cytosar-U®), pemetrexed (Alimta®). 53% of patients with breast cancers are AR positive. Treatments associated with response or lack of response/resistance when an AR positive mutation is found includes: bicalutamide (Casodex®), flutamide (Eulexin®), goserelin (Zoladex®), leuprolide (Lupron®), abarelix (Plenaxis®), gonadorelin (Factrel®).

* Biomarker status (overexpressed, underexpressed, positive or negative for specific mutations, etc.) determines whether that biomarker is associated with response, lack of response or resistance to each treatment.

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Pancreatic Cancer

Several biomarkers are associated with Pancreatic Cancer. These include, but are not limited to: KRAS, RRM1, SPARC, and TS. Of these biomarkers, a mutation in the KRAS - Kirsten murine Sarcoma gene and TS enzyme is usually a strong indicator.

29% of patients with gastric cancers have a high TS. Treatments associated with response or lack of response/resistance when a TS mutation is found includes: lack of response to 5-fluorouracil (Adrucil®), cytarabine (Cytosar-U®), pemetrexed (Alimta®).

* Biomarker status (overexpressed, underexpressed, positive or negative for specific mutations, etc.) determines whether that biomarker is associated with response, lack of response or resistance to each treatment.

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Skin Cancer

Several biomarkers are associated with Skin Cancer. These include, but are not limited to: BRAF, c-Kit, and SPARC. Of these biomarkers, a mutation in the BRAF - also know as v-raf murine sarcoma viral oncogene homolog B1 is a strong indicator. Sometimes the BRAF gene becomes mutated, which changes cell signaling along a pathway called MAP/ERK.

50-80% of patients with skin cancers have a BRAF mutation. When a cancer tests positive for a BRAF mutation, it can indicate a lack of response to panitumumab (Vectibix®) and cetuximab (Erbitux®), drugs that target another biomarker along the same pathway. 65% of patients with nervous system cancers have a BRAF mutation, 45% with thyroid cancer, 15% with colorectal cancer.

* Biomarker status (overexpressed, underexpressed, positive or negative for specific mutations, etc.) determines whether that biomarker is associated with response, lack of response or resistance to each treatment.

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Ovarian Cancer

Several biomarkers are associated with Ovarian Cancer. These include, but are not limited to: AR, BRCA1, c-MET, ER, ERCC1, HER2, PGP, PIK3CA, PR, TLE3, TOPO2A, and TUBB3. Of these biomarkers, a mutation in HER2 (Human Epidermal growth factor Receptor 2, also known as HER2/neu or ErbB-2) or AR (Androgen Receptor) is a strong indicator. While HER2 is a biomarker commonly associated with breast cancer. Significant percentages of patients have cancer originating in other parts of the body like the ovaries that also test positive for HER2.

11-40% of patients with ovarian cancers are HER2 positive. Research shows that these cancers may respond to treatments that target HER2 such as trastuzumab (Herceptin®) and lapatinib (Tykerb®). 30% of patients with ovarian cancers are AR positive. Treatments associated with response or lack of response/resistance when an AR positive mutation is found includes: bicalutamide (Casodex®), flutamide (Eulexin®), goserelin (Zoladex®), leuprolide (Lupron®), abarelix (Plenaxis®), gonadorelin (Factrel®).

* Biomarker status (overexpressed, underexpressed, positive or negative for specific mutations, etc.) determines whether that biomarker is associated with response, lack of response or resistance to each treatment.

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It’s estimated that a new article about cancer biomarker research is published every eight minutes. That’s how fast scientists are learning more about how cancer works on a molecular level. The bad news is that’s a lot of reading. The great news is that it’s already possible to apply much of this new cancer research to personalized treatment through molecular profiling.

This chart focuses on only a few cancer biomarkers — but, today, there are more than 80 biomarkers with potential for use in personalized cancer treatment today. And that number is constantly growing. (There are thousands of possible human disease biomarkers, the majority of which have no known use in cancer care.)